30 results on '"Riccardi, Carlo"'
Search Results
2. List of Contributors
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Antonelli, Alessandro, primary, Aslani, Saeed, additional, Ayuso, Teresa, additional, Aznar, Patricia, additional, Banik, Debarati, additional, Benvenga, Salvatore, additional, Beynon, Vanessa, additional, Bordron, Anne, additional, Brooks, Wesley H., additional, Cari, Luigi, additional, Carpenter, Susan, additional, Charras, Amandine, additional, Chiappinelli, Katherine B., additional, Coppedè, Fabio, additional, Costa-Reis, Patricia, additional, Covarrubias, Sergio, additional, Elia, Giusy, additional, Fallahi, Poupak, additional, Ferrari, Silvia Martina, additional, Garo, Lucien P., additional, Gay, Steffen, additional, Gerthoffer, William T., additional, Invernizzi, Pietro, additional, Jayaraman, Sundararajan, additional, Karouzakis, Emmanuel, additional, Klein, Kerstin, additional, Konsta, Orsia D., additional, Le Dantec, Christelle, additional, Leung, Yiu T., additional, Lleo, Ana, additional, Long, Hai, additional, Lu, Qianjin, additional, Mahmoudi, Mahdi, additional, Marzorati, Simona, additional, Mendioroz, Maite, additional, Migliorati, Graziella, additional, Murugaiyan, Gopal, additional, Nocentini, Giuseppe, additional, O’Reilly, Steven, additional, Prinjha, Rab K., additional, Ragusa, Francesca, additional, Ramelli, Sabrina, additional, Renaudineau, Yves, additional, Riccardi, Carlo, additional, Rioja, Inmaculada, additional, Sekiya, Takashi, additional, Sullivan, Kathleen E., additional, Tak, Paul-Peter, additional, Tough, David F., additional, Villagra, Alejandro, additional, Vita, Roberto, additional, Wang, Ling, additional, Yao, Zhi, additional, Yin, Heng, additional, Zhang, Rongxin, additional, and Zhang, Zimu, additional
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- 2018
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3. Treatment of Autoimmune Diseases and Prevention of Transplant Rejection and Graft-Versus-Host Disease by Regulatory T Cells: The State of the Art and Perspectives
- Author
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Nocentini, Giuseppe, primary, Cari, Luigi, additional, Migliorati, Graziella, additional, and Riccardi, Carlo, additional
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- 2018
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4. REGULATION BY INTERFERON AND T CELLS OF IL-2-DEPENDENT GROWTH OF NK PROGENITOR CELLS: A LIMITING DILUTION ANALYSIS
- Author
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Riccardi, Carlo, primary, Vose, B.M., additional, and Herberman, R.B., additional
- Published
- 1982
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5. REGULATION OF MOUSE NK ACTIVITY11These studies were supported by “Progretto Finalizzato Oncologia,” contract no. 84.00762.44 (U.O.: Riccardi) C.N.R. Rome, Italy.
- Author
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Riccardi, Carlo, primary, Migliorati, Graziella, additional, Giampietri, Antonio, additional, Ayroldi, Emira, additional, and Herberman, Ronald B., additional
- Published
- 1985
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6. Contributors
- Author
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Abb, Jochen, primary, Abo, Toru, additional, Acero, Raffaella, additional, Acha-Orbea, Hans, additional, Adams, Dolph O., additional, Adler, William H., additional, Ährlund-Richter, Lars, additional, Ahre, Anders, additional, Alberti, Saverio, additional, Allan, Jane E., additional, Allavena, Paola, additional, Allison, Anthony C., additional, Alsheikhly, Abdulrazzak, additional, Bernard Amos, D., additional, Andersson, Torbjörn, additional, Andrighetto, G., additional, Aoki, Tadao, additional, Aoyagi, Yoshitaka, additional, Argov, Shmuel, additional, Axberg, Inger, additional, Bach, Fritz H., additional, Bach, Jean-Francois, additional, Baines, Malcolm G., additional, Bakács, Tibor, additional, Balch, Charles M., additional, Bardos, Pierre, additional, Barlozzari, Teresa, additional, Bartlett, Scott P., additional, Bash, Jerry A., additional, Bechtold, Thomas, additional, Befus, Dean, additional, Bejarano, Maria T., additional, Benczur, Miklós, additional, Bennett, Michael, additional, Beran, Miroslav, additional, William Bere, E., additional, Berg, Kurt, additional, Biberfeldt, Peter, additional, Bienenstock, John, additional, Biondi, Andrea, additional, Biron, Christine A., additional, Bizière, Katleen, additional, Blomgren, Henric, additional, Bloom, Barry R., additional, Bloom, Eda T., additional, Bockman, Richard S., additional, Bolhuis, Reinder, additional, Bonavida, Benjamin, additional, Bonnard, G. D, additional, Boraschi, Diana, additional, Bordignon, Claudio, additional, Bottazzi, Barbara, additional, Bougnoux, Philippe, additional, Bradley, Thomas P., additional, Phillip Brandt, C., additional, Brooks, Colin G., additional, Brown, Garth W., additional, Brunda, Michael J., additional, Brunet, D., additional, Burgess, Donald E., additional, Burton, Robert C., additional, Caraux, Jean, additional, Carlson, George A., additional, Carpén, Olli, additional, Carpenter, Robin, additional, Caspani, Giorgio, additional, Cayre, Y., additional, Cesarmi, C., additional, Chang, Kenneth S.S., additional, Chang, Zong-liang, additional, Cheers, Christina, additional, Chow, Donna A., additional, Chung, Tae June, additional, Clagett, James A., additional, Clark, Edward A., additional, Cochran, Alistair J., additional, Colmenares, C., additional, Colombo, Nicoletta, additional, Cooper, Max D., additional, Cunningham-Rundles, Susanna, additional, Cupissol, Didier, additional, Cuttito, Michael, additional, D’Amore, Paula J., additional, Datta, Surjit K., additional, de Vries, Jan E., additional, Dean, J. H, additional, Degenne, Danielle, additional, Deinhardt, Friedrich, additional, Denn, Alfred C., additional, Dennert, Gunther, additional, Devlin, James J., additional, Dexter, David, additional, Djeu, Julie Y., additional, Dokhélar, Marie-Christine, additional, Domzig, Wolfgang, additional, Donati, Maria Benedetta, additional, Dupuy, Jean-Marie, additional, Edwards, Anne, additional, Efrati, Margalit, additional, Ehrlich, Rachel, additional, Ehrnst, Anneka, additional, Einhorn, Stefan, additional, Ellegaard, Jørgen, additional, Emmons, Sandra L., additional, Engler, Helmut, additional, Eugui, Elsie M., additional, Földes, Isrván, additional, Fagraeus, Astrid, additional, Fanning, Virginia, additional, Favier, Carine, additional, Favier, François, additional, Feng, Mei-fu, additional, Fernandes, Gabriel, additional, Ferrarini, Manlio, additional, Feucht, Helmut, additional, Figdor, Carl G., additional, Fischer, Dina G., additional, Fitzgerald, Patricia, additional, Forbes, James T., additional, Forget, Adrien, additional, Fredholm, Bertil, additional, Galatiuc, Cecilia, additional, Gallagher, Michael T., additional, Garam, Tamás, additional, Gherman, Maria, additional, Ghezzi, Pietro, additional, Gidlund, Magnus, additional, Gillis, Steven, additional, Goldfarb, Ronald H., additional, Golightly, Marc G., additional, Golub, Sidney, additional, Good, Robert A., additional, Gorelik, E., additional, Granger, Donald L., additional, Granger, Gale A., additional, Grayzel, Arthur I., additional, Anthony Greco, F., additional, Greenberg, Arnold H., additional, Grimberg, Alvar, additional, Gros, Philippe, additional, Groscurth, Peter, additional, Grossi, Carlo Enrico, additional, Grossman, Zvi, additional, Grundy (Chalmer), Jane E., additional, Gupta, Sudhir, additional, Gyódi, Éva, additional, Härfast, Bengt, additional, Habu, Sonoko, additional, Haliotis, Tina, additional, Hanna, Nabil, additional, Hansson, Mona, additional, Hapel, Andrew J., additional, Hatcher, Frank, additional, Hattori, Toshio, additional, Hatzfeld, A., additional, Haukaas, Sven, additional, Haynes, Barton F., additional, Hefeneider, Steven H., additional, Helfand, Stephen, additional, Hengartner, Hans, additional, Henney, Christopher S., additional, Herberman, R. B, additional, Heron, Iver, additional, Hersey, Peter, additional, Hibbs, John B., additional, Hoffman, Thomas, additional, Hokland, Marianne, additional, Hokland, Peter, additional, Holden, Howard T., additional, Hollán, Susan R., additional, Carmack Holmes, E., additional, Horikawa, Yon, additional, Hudig, Dorothy, additional, Huh, Nam Doll, additional, Ihle, James N., additional, Introna, Martino, additional, Ishizaka, Sally T., additional, Ishizaka, Teruko, additional, Jablonski, T., additional, Jensen, Pamela J., additional, Johansson, Bo, additional, Johnson, Donald R., additional, Johnson, William J., additional, Jondal, Mikael, additional, Kärre, Klas, additional, Kaiserlian, Dominique, additional, Kalland, Terje, additional, Kasai, Masataka, additional, Kaudewitz, Peter, additional, Kawase, Ichiro, additional, Kawate, Norihiko, additional, Kedar, Eli, additional, Keller, Robert, additional, Kiessling, Rolf, additional, Kim, Yoon Berm, additional, Kirchner, Holger, additional, Kirkpatrick, Dahlia, additional, Klein, Eva, additional, Klein, George, additional, Klein, Gunnar O., additional, Kleinerman, Eugenie S., additional, Kolb, Jean Pierre, additional, Kongshavn, Patricia A.L., additional, Koo, G. C, additional, Koren, Hillel S., additional, Kraft, Dietrich, additional, Kubota, Richard, additional, Kuhn, Raymond E., additional, Kumar, Vinay, additional, Kung, Patrick C., additional, Kurashige, Takanobu, additional, Kuribayashi, Kagemasa, additional, Kusaimi, Nuha T., additional, Landolfo, Santo, additional, Lanefeldt, Fred, additional, Lang, Rosmarie, additional, Lanza, Emanuela, additional, Laskay, Tamás, additional, Lattime, Edmund C., additional, Lavie, Gad, additional, Ledbetter, Jeffrey A., additional, Leung, Kam H., additional, Levy, Elinor M., additional, Lindsten, Tullia, additional, Lipinski, Marc, additional, Lohmann-Matthes, Marie-Luise, additional, Lohmeyer, Jürgen, additional, Longhi, Bernard, additional, Lopez, Carlos, additional, Lotzová, Eva, additional, Luck, Anne, additional, Luini, Walter, additional, Lust, John A., additional, Macgeorge, Jenny, additional, Malatzky, Elinor, additional, Maluish, Annette E., additional, Manciulea, Moiara, additional, Mandeville, Rosemonde, additional, Mantovani, Alberto, additional, Marchmont, R. J, additional, Martinetto, Pancrazio, additional, Martinotti, Giovanna, additional, Masucci, Giuseppe, additional, Masucci, Maria G., additional, Masuda, Aoi, additional, Matzku, S., additional, McCarthy, William, additional, Olga McDaniel, D., additional, McGarry, Ronald C., additional, Mellen, P. F, additional, Mellstedt, Håkan, additional, Merrill, Jean E., additional, Micksche, Michael, additional, Miller, Aaron E., additional, Miller, V., additional, Milton, Gerald, additional, Minato, Nagahiro, additional, Miner, Karen M., additional, Minning, Lory, additional, Mittl, L. R, additional, Miyakoshi, Hideo, additional, Mizukoshi, Mikio, additional, Molina, Pierangela, additional, Moore, M., additional, Morgan, Doris, additional, Muchmore, Andrew V., additional, Murphy, Edwin D., additional, Murphy, Juneann, additional, Muse, Kenneth E., additional, Musset, Mircea, additional, Nasrallah, Anthony G., additional, Neefe, John R., additional, Andrew Neighbour, P., additional, Newman, Walter, additional, Niitsuma, Masayuki, additional, Nilsson, Kennith, additional, Norrby, Erling, additional, Nose, Masato, additional, Obexer, Gerhard, additional, Oeltmann, Thomas N., additional, Okumura, Ko, additional, Olabuenaga, Susana, additional, Örvell, Claes, additional, Ortaldo, John R., additional, Pálffy, György, additional, Pape, Gerd R., additional, Pasqualetto, Elena, additional, Patarroyo, Manuel, additional, Pecoraro, Gene A., additional, Peius, Louis M., additional, Peppard, J. R, additional, Peri, Giuseppe, additional, Perlmann, Peter, additional, Perussia, Bice, additional, Pestka, Sidney, additional, Petrányi, Győső, additional, Piontek, Gerald E., additional, Platsoucas, Chris D., additional, Pohajdak, B., additional, Polentarutti, Nadia, additional, Pollack, Sylvia B., additional, Ponzio, Nicholas M., additional, Priest, Elizabeth L., additional, Pross, Hugh, additional, Pulay, Tamás, additional, Purtillo, David T., additional, Pyle, Robert S., additional, Quan, Phuc-Canh, additional, Ramsey, Keith M., additional, Redelman, Doug, additional, Rees, Robert, additional, Reinitz, Elizabeth, additional, Renoux, Gérard, additional, Renoux, Micheline, additional, Rey, Augustin, additional, Reynolds, Craig W., additional, Riccardi, Carlo, additional, Rieber, Ernst Peter, additional, Riethmüller, Gert, additional, Ringwald, Gábor, additional, Rocheleau, Normand, additional, Roder, John C., additional, Rosen, B., additional, Rosenthal, Kendall L., additional, Roths, John B., additional, Rotilio, Domenico, additional, Rubin, Berish Y., additional, Rubin, Peter, additional, Ruebush, Mary J., additional, Rumpold, Helmut, additional, Saksela, Eero, additional, Salmona, Mario, additional, Santoni, Angela, additional, Savary, C. A, additional, Saxena, Queen B., additional, Saxena, Rajiv K., additional, Schindler, Liesel, additional, Schlimok, Günter, additional, Schreiber, Hans, additional, Seeley, Janet K., additional, Senik, Anna, additional, Serrate, Susana A., additional, Serrou, Bernard, additional, Sharrow, Susan O., additional, Shellam, Geoffrey R., additional, Shibata, Akira, additional, Shimamura, Kazuo, additional, Siegal, Frederick P., additional, Skamene, Emil, additional, Somers, Scott D., additional, Spits, Hergen, additional, Stoger, Ivana, additional, Stadler, Beda M., additional, Stevenson, Mary M., additional, Stitz, Lothar, additional, Strander, Hans, additional, Stutman, Osias, additional, Sulica, Andrei, additional, Sun, Deming, additional, Svastits, Egon, additional, Tagliabue, Aldo, additional, Takasugi, Mitsuo, additional, Tálas, Margarita, additional, Tanaka, Kenichi, additional, Taramelli, Donatella, additional, Targan, Stephan R., additional, Tarkkanen, Jussi, additional, Thiel, Eckardt, additional, Timonen, Tuomo, additional, Tótpál, Klára, additional, Tötterman, Thomas, additional, Trentin, John J., additional, Trinchieri, Giorgio, additional, Tursz, Thomas, additional, Uchida, Atsushi, additional, Ullberg, Mans, additional, Urban, James, additional, Urdal, David L., additional, Vánky, Farkas, additional, Varesio, Luigi, additional, Varga, Miklòs, additional, Virtanen, Ismo, additional, Vose, B. M, additional, Ward, Jerrold M., additional, Weiel, James E., additional, Weigle, William O., additional, Weitzen, Monica L., additional, Welsh, Raymond M., additional, Werkmeister, Jerome A., additional, Weston, Patricia A., additional, Wigzell, H., additional, Wiltrout, R., additional, Windsor, Nancy T., additional, Winn, Henry J., additional, Witz, Isaac P., additional, Woody, James N., additional, Wright, Susan C., additional, Yamamoto, Robert S., additional, Yogeeswaran, Ganesa, additional, Zöller, M., additional, Zagury, Daniel, additional, Zander, Helmut, additional, Zarling, Joyce M., additional, Zawatzky, Rainer, additional, and Loems Ziegler, Hans-Werner, additional
- Published
- 1982
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7. INHIBITION AS WELL AS AUGMENTATION OF MOUSE NK ACTIVITY BY PYRAN COPOLYMER AND ADRIAMYCIN
- Author
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Santoni, Angela, primary, Riccardi, Carlo, additional, Barlozzari, T., additional, and Herberman, Ronald B., additional
- Published
- 1980
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8. INTERFERON AND NK CELLS
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Herberman, Ronald B., primary, Ortaldo, John R., additional, Riccardi, Carlo, additional, Timonen, Tuomo, additional, Schmidt, Azriel, additional, Maluish, Annette, additional, and Djeu, Julie, additional
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- 1982
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9. CLONED LINES OF MOUSE NATURAL KILLER CELLS
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Riccardi, Carlo, primary, Allavena, Paola, additional, Ortaldo, John R., additional, and Herberman, Ronald B., additional
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- 1982
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10. C. PARVUM-INDUCED SUPPRESSOR CELLS FOR MOUSE NK ACTIVITY
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Santoni, Angela, primary, Riccardi, Carlo, additional, Barlozzari, Teresa, additional, and Herberman, Ronald B., additional
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- 1982
- Full Text
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11. Glucocorticoids and COVID-19.
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Bruscoli S, Puzzovio PG, Zaimi M, Tiligada K, Levi-Schaffer F, and Riccardi C
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- Humans, Glucocorticoids therapeutic use, Glucocorticoids pharmacology, Anti-Inflammatory Agents adverse effects, Autoimmune Diseases drug therapy, COVID-19 Drug Treatment
- Abstract
Coronavirus Disease 19 (COVID-19) is associated with high morbidity and mortality rates globally, representing the greatest health and economic challenge today. Several drugs are currently approved for the treatment of COVID-19. Among these, glucocorticoids (GCs) have received particular attention due to their anti-inflammatory and immunosuppressive effects. In fact, GC are widely used in current clinical practice to treat inflammatory, allergic and autoimmune diseases. Major mechanisms of GC action include inhibition of innate and adaptive immune activity. In particular, an important role is played by the inhibition of pro-inflammatory cytokines and chemokines, and the induction of proteins with anti-inflammatory activity. Overall, as indicated by various national and international regulatory agencies, GCs are recommended for the treatment of COVID-19 in patients requiring oxygen therapy, with or without mechanical ventilation. Regarding the use of GCs for the COVID-19 treatment of non-hospitalized patients at an early stage of the disease, many controversial studies have been reported and regulatory agencies have not recommended their use. The decision to start GC therapy should be based not only on the severity of COVID-19 disease, but also on careful considerations of the benefit/risk profile in individual patients, including monitoring of adverse events. In this review we summarize the effects of GCs on the major cellular and molecular components of the inflammatory/immune system, the benefits and the adverse common reactions in the treatment of inflammatory/autoimmune diseases, as well as in the management of COVID-19., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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12. The novel role of glucocorticoid-induced leucine zipper as a marker of mucosal healing in inflammatory bowel diseases.
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Leoncini G, Gentili M, Lusenti E, Caruso L, Calafà C, Migliorati G, Riccardi C, Villanacci V, and Ronchetti S
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- Biomarkers, Humans, Inflammation, Leucine Zippers, Mucous Membrane, Retrospective Studies, Transcription Factors metabolism, Glucocorticoids pharmacology, Inflammatory Bowel Diseases drug therapy
- Abstract
Glucocorticoid-induced leucin zipper (GILZ) mediates the effects of glucocorticoids in immune cells, but little is known about its role in both the gastro-intestinal (GI) mucosa and inflammatory bowel diseases (IBD) in humans. To investigate the GILZ protein expression profile in the GI tract, mucosal biopsies from 80 patients were retrospectively enrolled in this study and subdivided into three groups: 1) patients without clinical-endoscopic and histological evidence of IBD; 2) IBD patients; 3) patients with chronic atrophic gastritis (CAG) and Barrett esophagus (BE), both characterized by intestinal metaplasia (IM). GILZ expression was assessed by immunohistochemical and immunofluorescence methods. Our results showed that GILZ protein was strongly expressed in the secretory cells in healthy mucosa. GILZ expression was reduced in goblet cells in active disease, whereas it was restored in quiescent diseases. Conversely, entero-endocrine cells were not involved in such inflammation-driven dynamics, as GILZ expression remained detectable in active disease. Moreover, GILZ was expressed in IM, but was limited to CAG, and was not detected in BE. In summary, GILZ acts as a secretory protein in the GI mucosa in healthy, hyperplastic and metaplastic conditions. Its secretion by goblet cells is mostly affected by neutrophils mucosal infiltration and seems to be directly related to active mucosal inflammation in IBD. Overall, our findings suggest that GILZ is a suitable molecule to be considered as a histological marker of mucosal healing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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13. Glucocorticoid-induced leucine zipper modulates macrophage polarization and apoptotic cell clearance.
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Vago JP, Galvão I, Negreiros-Lima GL, Teixeira LCR, Lima KM, Sugimoto MA, Moreira IZ, Jones SA, Lang T, Riccardi C, Teixeira MM, Harris J, Morand EF, and Sousa LP
- Subjects
- Animals, Bone Marrow Cells drug effects, Cell Migration Assays, Leukocyte, Cell Physiological Phenomena drug effects, Gene Expression Regulation drug effects, Inflammation chemically induced, Inflammation pathology, Leukocyte Count, Lipopolysaccharides pharmacology, Macrophages drug effects, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Pleural Cavity cytology, Apoptosis drug effects, Glucocorticoids pharmacology, Transcription Factors drug effects
- Abstract
Macrophages are professional phagocytes that display remarkable plasticity, with a range of phenotypes that can be broadly characterized by the M1/M2 dichotomy. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a protein known to mediate anti-inflammatory and some pro-resolving actions, including as neutrophil apoptosis. However, the role of GILZ in key macrophage function is not well understood. Here, we investigated the role of GILZ on macrophage reprogramming and efferocytosis. Using murine bone-marrow-derived macrophages (BMDMs), we found that GILZ was expressed in naive BMDMs and exhibited increased expression in M2-like macrophages (IL4-differentiated). M1-like macrophages (IFN/LPS-differentiated) from GILZ
-/- mice showed higher expression of the M1 markers CD86, MHC class II, iNOS, IL-6 and TNF-α, associated with increased levels of phosphorylated STAT1 and lower IL-10 levels, compared to M1-differentiated cells from WT mice. There were no changes in the M2 markers CD206 and arginase-1 in macrophages from GILZ-/- mice differentiated with IL-4, compared to cells from WT animals. Treatment of M1-like macrophages with TAT-GILZ, a cell-permeable GILZ fusion protein, decreased the levels of CD86 and MHC class II in M1-like macrophages without modifying CD206 levels in M2-like macrophages. In line with the in vitro data, increased numbers of M1-like macrophages were found into the pleural cavity of GILZ-/- mice after LPS-injection, compared to WT mice. Moreover, efferocytosis was defective in the context of GILZ deficiency, both in vitro and in vivo. Conversely, treatment of LPS-injected mice with TAT-GILZ promoted inflammation resolution, associated with lower numbers of M1-like macrophages and increased efferocytosis. Collectively, these data indicate that GILZ is a regulator of important macrophage functions, contributing to macrophage reprogramming and efferocytosis, both key steps for the resolution of inflammation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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14. Molecular mechanisms underlying eicosapentaenoic acid inhibition of HDAC1 and DNMT expression and activity in carcinoma cells.
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Ceccarelli V, Ronchetti S, Marchetti MC, Calvitti M, Riccardi C, Grignani F, and Vecchini A
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- Animals, Cell Line, Tumor, CpG Islands, DNA metabolism, DNA (Cytosine-5-)-Methyltransferase 1 metabolism, Genes, Tumor Suppressor, Histone Deacetylase 1 metabolism, Kruppel-Like Transcription Factors biosynthesis, Kruppel-Like Transcription Factors genetics, Liver Neoplasms, Experimental genetics, Liver Neoplasms, Experimental metabolism, PPAR gamma metabolism, Rats, Antineoplastic Agents pharmacology, DNA (Cytosine-5-)-Methyltransferase 1 antagonists & inhibitors, Eicosapentaenoic Acid pharmacology, Epigenesis, Genetic drug effects, Gene Expression Regulation, Neoplastic drug effects, Histone Deacetylase 1 antagonists & inhibitors
- Abstract
DNA methylation and histone acetylation, the most studied epigenetic changes, drive and maintain cancer phenotypes. DNA methyltransferase (DNMT) dysregulation promoted localized hypermethylation in CpG rich regions while upregulated histone deacetylases (HDAC) deacetylated histone tails. Both changes led to close chromatin conformation, suppressing transcription and silencing tumor suppressor genes. Consequently, HDAC and DNMT inhibitors appeared to reprogram the transcriptional circuit and potentiate anti-tumoral activity. Here, we report that eicosapentaenoic acid (EPA), a fatty acid with anti-cancer properties, inhibited HDAC1 and DNMT expression and activity, thus promoting tumor suppressor gene expression. In hepatocarcinoma cells (HCC) EPA bound and activated PPARγ thus downregulating HDAC1 which sequentially reduced expression of DNMT1, 3A and 3B. At the same time, activated PPARγ physically interacted with DNMT1 and HDAC1 in a CpG island on the Hic-1 gene to assemble PPARγ/DNMT1 and PPARγ/HDAC1 protein complexes, which exited from DNA. When EPA and PPARγ were no longer bound, the protein complexes separated into individual proteins. Consequently, DNMT1 and HDAC1 down-regulation and release from DNA inhibited their activities. Overall, EPA-bound PPARγ induced re-expression of the tumor suppressor gene Hic-1. In the present study PPARγ emerged as a master regulator acting synergistically through diverse targets and ways to reveal the epigenetic action of EPA as an HDAC1 and DNMT1 inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Disclosures All authors disclose any potential conflicts (financial, professional, or personal) that are relevant to the manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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15. Selective CB2 inverse agonist JTE907 drives T cell differentiation towards a Treg cell phenotype and ameliorates inflammation in a mouse model of inflammatory bowel disease.
- Author
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Gentili M, Ronchetti S, Ricci E, Di Paola R, Gugliandolo E, Cuzzocrea S, Bereshchenko O, Migliorati G, and Riccardi C
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- Animals, Cell Differentiation, Colitis pathology, Colon drug effects, Colon pathology, Cytokines immunology, Disease Models, Animal, Inflammation immunology, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases pathology, Male, Mice, Inbred C57BL, Phenotype, Spleen cytology, T-Lymphocytes cytology, T-Lymphocytes immunology, Anti-Inflammatory Agents pharmacology, Colitis immunology, Dioxoles pharmacology, Quinolones pharmacology, Receptor, Cannabinoid, CB2 immunology, T-Lymphocytes drug effects
- Abstract
Cannabinoids are known to possess anti-inflammatory and immunomodulatory properties, but the mechanisms involved are not fully understood. CB2 is the cannabinoid receptor that is expressed primarily on hematopoietic cells and mediates the immunoregulatory functions of cannabinoids. In order to study the effect of JTE907, a selective/inverse agonist of CB2 with anti-inflammatory properties, on the differentiation of T cell subtypes, we used an in vitro system of Th lineage-specific differentiation of naïve CD4
+ T lymphocytes isolated from the mouse spleen. The results indicate that JTE907 was able to induce the differentiation of Th0 cells into the Treg cell phenotype, which was characterized by the expression of FoxP3, TGF-β and IL-10. P38 phosphorylation and STAT5A activation were found to mediate the signaling pathway triggered by JTE907 via the CB2 receptor in Th0 lymphocytes. In mice with DNBS-induced colitis, JTE907 treatment was able to induce an increase in the number of CD4+ CD25+ FoxP3+ cells in the lamina propria after 24 h of disease onset and reduce disease severity after 48 h. Further, longer JTE907 treatment resulted in less severe colitis even when administered orally, resulting in less body weight loss, reduction of the disease score, prevention of NF-κB activation, and reduction of the expression of adhesion molecules. Collectively, the results of this study indicate that specific signals delivered through the CB2 receptor can drive the immune response towards the Treg cell phenotype. Thus, ligands such as JTE907 may have use as potential therapeutic agents in autoimmune and inflammatory diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2019
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16. A focused Real Time PCR strategy to determine GILZ expression in mouse tissues.
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Cari L, Ricci E, Gentili M, Petrillo MG, Ayroldi E, Ronchetti S, Nocentini G, and Riccardi C
- Abstract
Glucocorticoid-Induced Leucine Zipper (GILZ) is a glucocorticoid-inducible gene that mediates glucocorticoid anti-inflammatory effects. GILZ and the isoform L-GILZ are expressed in a variety of cell types, especially of hematopoietic origin, including macrophages, lymphocytes and epithelial cells, and strongly upregulated upon glucocorticoid treatment. A quantitative analysis of GILZ expression in mouse tissues is technically difficult to perform because of the presence of a pseudogene and the high homology of GILZ gene with other genes of TSC22 family. We here propose specific primer pairs to be used in Real Time PCR to avoid unwanted amplification of GILZ pseudogene and TSC-22 family member d1iso3. These primer pairs were used to determine GILZ and L-GILZ expression, in either untreated or in vivo and in vitro dexamethasone-treated tissues. Results indicate that GILZ and L-GILZ are upregulated by glucocorticoids, being GILZ more sensitive to glucocorticoid induction than L-GILZ, but they are differently expressed in all examined tissues, confirming a different role in specific cells. An inappropriate primer pair amplified also GILZ pseudogene and TSC22d1iso3, thus producing misleading results. This quantitative evaluation may be used to better characterize the role of GILZ and L-GILZ in mice and may be translated to humans.
- Published
- 2015
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17. Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice.
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Bruscoli S, Biagioli M, Sorcini D, Frammartino T, Cimino M, Sportoletti P, Mazzon E, Bereshchenko O, and Riccardi C
- Subjects
- Animals, Blotting, Western, Cell Proliferation drug effects, Cells, Cultured, Flow Cytometry, Lymphocytosis etiology, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Apoptosis drug effects, B-Lymphocytes pathology, Glucocorticoids pharmacology, Lymphocytosis pathology, Transcription Factors physiology
- Abstract
Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecular mechanisms of GC action include induction of GC target genes. Glucocorticoid-induced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethal B lymphocytosis, with expansion of B220(+) cells in the bone marrow and in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF-κB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders., (© 2015 by The American Society of Hematology.)
- Published
- 2015
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18. GITR+ regulatory T cells in the treatment of autoimmune diseases.
- Author
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Petrillo MG, Ronchetti S, Ricci E, Alunno A, Gerli R, Nocentini G, and Riccardi C
- Subjects
- Animals, Autoimmune Diseases therapy, Cell Differentiation, Disease Progression, Humans, Interleukin-2 Receptor alpha Subunit immunology, T-Lymphocytes, Regulatory cytology, Autoimmune Diseases immunology, Glucocorticoid-Induced TNFR-Related Protein immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Autoimmune diseases decrease life expectancy and quality of life for millions of women and men. Although treatments can slow disease progression and improve quality of life, all currently available drugs have adverse effects and none of them are curative; therefore, requiring patients to take immunosuppressive drugs for the remainder of their lives. A curative therapy that is safe and effective is urgently needed. We believe that therapies promoting the in vivo expansion of regulatory T cells (Tregs) or injection of in vitro expanded autologous/heterologous Tregs (cellular therapy) can alter the natural history of autoimmune diseases. In this review, we present data from murine and human studies suggesting that 1) glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) plays a crucial role in thymic Treg (tTreg) differentiation and expansion; 2) GITR plays a crucial role in peripheral Treg (pTreg) expansion; 3) in patients with Sjögren syndrome and systemic lupus erythematosus, CD4(+)GITR(+) pTregs are expanded in patients with milder forms of the disease; and 4) GITR is superior to other cell surface markers to differentiate Tregs from other CD4(+) T cells. In this context, we consider two potential new approaches for treating autoimmune diseases consisting of the in vivo expansion of GITR(+) Tregs by GITR-triggering drugs and in vitro expansion of autologous or heterologous GITR(+) Tregs to be infused in patients. Advantages of such an approach, technical problems, and safety issues are discussed., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2015
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19. Silymarin suppress CD4+ T cell activation and proliferation: effects on NF-kappaB activity and IL-2 production.
- Author
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Gharagozloo M, Velardi E, Bruscoli S, Agostini M, Di Sante M, Donato V, Amirghofran Z, and Riccardi C
- Subjects
- Animals, Annexin A5, Biotransformation drug effects, Blotting, Western, Cell Death drug effects, Cell Proliferation drug effects, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Mice, Mice, Inbred C57BL, Protein Transport drug effects, Spleen cytology, Transcription Factor RelA metabolism, CD4-Positive T-Lymphocytes drug effects, Immunologic Factors, Interleukin-2 biosynthesis, Lymphocyte Activation drug effects, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Silymarin pharmacology
- Abstract
Silymarin, a mixture of bioactive flavonolignans isolated from Silybum marianum, exhibits anti-carcinogenic, anti-inflammatory and cytoprotective effects. In this study, the in vitro immunomodulatory activity of silymarin was investigated using CD4+ splenocytes from C57/Bl6 mice. Proliferation assay revealed that silymarin, at 50 microM concentration, significantly inhibited CD4+ cells proliferation. ELISA analyses indicated that silymarin significantly inhibited IL-2 and IFN-gamma production. Immunofluorescence staining performed on the mouse hybridoma T cell line (3DO) revealed a block of nuclear translocation of transcription factor kappaB (NF-kappaB), which is known to be responsible for IL-2 transcriptional activation. Moreover, silymarin inhibited p65/NF-kappaB phosphorylation in CD4+ T cell. These results suggest that silymarin is able to inhibit T cell activation and proliferation, notably acting on pathways of NF-kappaB activation/translocation., ((c) 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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20. Identification of regulatory T cells in systemic lupus erythematosus.
- Author
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Gerli R, Nocentini G, Alunno A, Bocci EB, Bianchini R, Bistoni O, and Riccardi C
- Subjects
- Animals, Antigens, Differentiation genetics, Antigens, Differentiation immunology, CD4 Antigens, Forkhead Transcription Factors genetics, Forkhead Transcription Factors immunology, Glucocorticoid-Induced TNFR-Related Protein, Humans, Immune Tolerance immunology, Interleukin-17 immunology, Interleukin-2 Receptor alpha Subunit biosynthesis, Interleukin-2 Receptor alpha Subunit genetics, Interleukin-2 Receptor alpha Subunit immunology, Lupus Erythematosus, Systemic immunology, Lupus Erythematosus, Systemic metabolism, Mice, Receptors, Nerve Growth Factor genetics, Receptors, Nerve Growth Factor immunology, Receptors, Tumor Necrosis Factor genetics, Receptors, Tumor Necrosis Factor immunology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory pathology, Th1 Cells immunology, Th2 Cells immunology, Antigens, Differentiation metabolism, Forkhead Transcription Factors metabolism, Lupus Erythematosus, Systemic pathology, Receptors, Nerve Growth Factor metabolism, Receptors, Tumor Necrosis Factor metabolism, T-Lymphocytes, Regulatory metabolism
- Abstract
The concept that regulatory T cells (Treg) play a key role in both development and maintenance of autoimmune response in rheumatic diseases is well accepted. In recent years, several studies analyzed Treg cell phenotype and function in systemic lupus erythematosus (SLE), the prototypical systemic autoimmune disorder in humans. Although qualitative and/or quantitative abnormalities of Treg cells have been shown, data are often conflicting. This may depend on the selection of patients with different degrees of disease activity or on immunosuppressive treatments that can alter Treg cell findings. Among several proposed surface or intracellular Treg cell markers, CD25 at high level of expression and the transcription factor Foxp3 are the two most investigated in SLE. Despite the glucocorticoid-induced TNF receptor-related protein (GITR) represents a reliable phenotypic marker of murine Treg cells, little is known about its role in humans, in particular in the course of systemic autoimmune disorders. Preliminary data seems to suggest that this marker may represent a good tool to identify cell populations included within Treg cell subsets.
- Published
- 2009
- Full Text
- View/download PDF
21. The GITRL-GITR system alters TLR-4 expression on DC during fungal infection.
- Author
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Vecchiarelli A, Pericolini E, Gabrielli E, Agostini M, Bistoni F, Nocentini G, Cenci E, and Riccardi C
- Subjects
- Animals, B7-1 Antigen immunology, B7-1 Antigen metabolism, CD28 Antigens immunology, CD28 Antigens metabolism, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes microbiology, CD40 Antigens immunology, CD40 Antigens metabolism, Candida albicans immunology, Candidiasis microbiology, Dendritic Cells metabolism, Dendritic Cells microbiology, Glucocorticoid-Induced TNFR-Related Protein, Interferon-gamma biosynthesis, Interferon-gamma immunology, Interleukin-2 biosynthesis, Interleukin-2 immunology, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 immunology, Myeloid Differentiation Factor 88 metabolism, Receptors, Nerve Growth Factor genetics, Receptors, Nerve Growth Factor immunology, Receptors, Tumor Necrosis Factor genetics, Receptors, Tumor Necrosis Factor immunology, Toll-Like Receptor 2 immunology, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 immunology, Toll-Like Receptor 4 metabolism, Tumor Necrosis Factors immunology, CD4-Positive T-Lymphocytes immunology, Candidiasis immunology, Dendritic Cells immunology, Receptors, Nerve Growth Factor metabolism, Receptors, Tumor Necrosis Factor metabolism, Tumor Necrosis Factors metabolism
- Abstract
The glucocorticoid-induced TNFR-related (GITR) protein is a member of the tumor necrosis factor receptor superfamily influencing natural and acquired immune response. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting cells. Previously, we demonstrated that GITR plays a role in regulating immune response to Candida albicans. Here we analyzed whether GITRL-GITR interaction influences the recognition of C. albicans by regulating the expression of pattern recognition receptors on splenic dendritic cells. Our report demonstrates that under physiological conditions and during candidiasis the GITRL-GITR system affects TLR-2 and TLR-4 expression on DC. These changes correlate with decrease in: MyD88 activation; CD80 and CD40 expression on DC; T cell activation response, including CD28 expression, IL-2 and IFN-gamma production. Our results point out that, during fungal infection, GITRL-GITR interaction modulates TLR-4 and TLR-2 expression, thereby altering the antigen presentation process, and suggesting a role of GITRL-GITR interaction in resistance against infectious diseases.
- Published
- 2009
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22. Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines.
- Author
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Cannarile L, Fallarino F, Agostini M, Cuzzocrea S, Mazzon E, Vacca C, Genovese T, Migliorati G, Ayroldi E, and Riccardi C
- Subjects
- Animals, Bleomycin administration & dosage, Bleomycin adverse effects, Cell Differentiation genetics, Cell Differentiation immunology, Dexamethasone administration & dosage, GATA3 Transcription Factor immunology, Hypersensitivity, Delayed genetics, Hypersensitivity, Delayed immunology, Immunologic Factors administration & dosage, Mice, Mice, Transgenic, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis immunology, Pulmonary Fibrosis pathology, STAT6 Transcription Factor immunology, Transcription Factors genetics, Transgenes genetics, Up-Regulation genetics, Cytokines immunology, Th2 Cells immunology, Transcription Factors immunology, Transgenes immunology, Up-Regulation immunology
- Abstract
GILZ (glucocorticoid-induced leucine zipper), a gene induced by dexamethasone, is involved in control of T lymphocyte activation and apoptosis. In the present study, using Gilz transgenic mice (TG), which overexpress GILZ in the T-cell lineage, we demonstrate that Gilz is implicated in T helper-2 (Th-2) response development. After in vitro stimulation by CD3/CD28 antibodies, peripheral naive CD4+ T cells from TG mice secrete more Th-2 cytokines such as interleukin-4 (IL-4), IL-5, IL-13, and IL-10, and produce less Th-1 cytokines such as interferon-gamma (IFN-gamma) than wild-type mice (WT). CD4+ TG lymphocytes up-regulated Th-2 cytokine expression in the specific response to ovalbumin chicken egg (OVA) antigen immunization. Up-regulation correlated with increased expression of GATA-3 and signal transducer and activator of transcription 6 (Stat6), Th-2-specific transcription factors and decreased expression of T-bet, a transcription factor involved in Th-1 differentiation. Finally, in TG mice delayed-type hypersensitivity, a Th-1 response, was inhibited and bleomycin-induced pulmonary fibrosis, a Th-2 mediated disease, was more severe. These results indicate that Gilz contributes to CD4+ commitment toward a Th-2 phenotype and suggest this contribution may be another mechanism accounting for glucocorticoid immunomodulation.
- Published
- 2006
- Full Text
- View/download PDF
23. Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice.
- Author
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Delfino DV, Agostini M, Spinicelli S, Vito P, and Riccardi C
- Subjects
- Animals, Apoptosis, CD2 Antigens genetics, Caspase 3, Caspase 8, Caspases metabolism, Cell Culture Techniques, DNA Replication, Glucocorticoids pharmacology, Humans, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, RNA, Messenger genetics, Thymus Gland immunology, T-Lymphocytes immunology, Transcription Factors immunology
- Abstract
Glucocorticoids promote thymocyte apoptosis and modulate transcription of numerous genes. GILZ (glucocorticoid-induced leucine zipper), being one of them, is strongly up-regulated in the thymus. To elucidate its function we generated transgenic mice overexpressing it specifically in the T-cell lineage and characterized its influence on thymus function. In young adult transgenic mice CD4(+)CD8(+) thymocyte number was significantly decreased and ex vivo thymocyte apoptosis was increased. Apoptotic pathway analysis detected reduced antiapoptotic B-cell leukemia XL (Bcl-xL) expression and increased activation of caspase-8 and caspase-3. Time-course experiments showed that in wild-type (WT) thymocytes GILZ up-regulation was followed by sequential Bcl-xL decreased expression and activation of caspase-8 and of caspase-3. Moreover, GILZ delivered inside WT thymocytes by a fusion protein with the transactivator of transcription (TAT) peptide decreased Bcl-xL and promoted their apoptosis. In aged mice perturbation of thymic subset numbers was amplified over time, as demonstrated by a further decrease in CD4(+)CD8(+) cells and increases in CD4(+)CD8(-), CD4(-)CD8(-), and CD8(+)CD4(-) cell counts. These results support the hypothesis that GILZ participates in the regulation of thymocyte apoptosis by glucocorticoids.
- Published
- 2004
- Full Text
- View/download PDF
24. Synthesis and evaluation of anti-apoptotic activity of L-carnitine cyclic analogues and amino acid derivatives.
- Author
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Fringuelli R, Utrilla Navarro MP, Milanese L, Bruscoli S, Schiaffella F, Riccardi C, and De Simone C
- Subjects
- Amino Acids chemical synthesis, Amino Acids pharmacology, Apoptosis physiology, Carnitine analogs & derivatives, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical methods, Humans, Jurkat Cells, Apoptosis drug effects, Carnitine chemical synthesis, Carnitine pharmacology
- Abstract
Two series of derivatives were synthesised. In one series (R)-4-hydroxy-2-pyrrolidinone was used as a mimic of cyclic L-carnitine analogue and in the second series 3-amino-2-piperidinone was used as a cyclic ornithine analogue. N-Benzyloxycarbonyl derivatives of some amino acids were also prepared. The newly synthesised compounds were tested for their ability to inhibit Fas-activated apoptosis of human Jurkatt T-cell line. The results confirm the previously described anti-apoptotic activity of carnitine and indicate new carnitine and amino acid analogues (1, 3, 6, 7, 20) that inhibit Fas-induced apoptosis.
- Published
- 2004
- Full Text
- View/download PDF
25. Sphingolipids and the immune system.
- Author
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Cinque B, Di Marzio L, Centi C, Di Rocco C, Riccardi C, and Grazia Cifone M
- Subjects
- Animals, Ceramides immunology, Sphingolipids metabolism, Immune System physiology, Leukocytes physiology, Sphingolipids immunology
- Abstract
The importance of sphingolipids, not only as components of plasma membranes but also as key players in different physiological and pathophysiological cellular events, is now emerging. This review gathers together what the authors feel are the most relevant data, present in the literature, regarding the roles and the effects of sphingolipids, such as ceramide, ceramide-1-phosphate (C1P), sphingosine (SP) and sphingosine-1-phosphate (S1P), on the development, activation and regulation of the immune system.
- Published
- 2003
- Full Text
- View/download PDF
26. Dexamethasone-induced thymocytes apoptosis requires glucocorticoid receptor nuclear translocation but not mitochondrial membrane potential transition.
- Author
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Marchetti MC, Marco BD, Santini MC, Bartoli A, Delfino DV, and Riccardi C
- Subjects
- Animals, Caspase 3, Caspases metabolism, Enzyme Activation drug effects, Mitochondria metabolism, Protein Transport drug effects, Thymus Gland cytology, Thymus Gland metabolism, Apoptosis drug effects, Cell Nucleus metabolism, Dexamethasone pharmacology, Membrane Potentials drug effects, Mitochondria drug effects, Receptors, Glucocorticoid metabolism, Thymus Gland drug effects
- Abstract
Dexamethasone (DEX), a glucocorticoid hormone (GCH) with specificity for the glucocorticoid receptor (GR) induces T lymphocyte and thymocyte apoptosis. DEX-activated thymocyte apoptosis requires a sequence of biochemical events including mRNA and protein synthesis. In particular, GCH treatment induces non-genomic mechanisms, such as for example Ca(2+) mobilization and PI-PLC activation, and genomic mechanisms. Most of these events, including protein synthesis, are required and precede caspase activation. As protein synthesis is required for caspases and apoptosis activation, DEX-induced GR nuclear translocation is necessary for apoptosis. Cell treatment with geldanamycin (GA) inhibits the GR nuclear translocation and consequently, caspases activation and apoptosis. Although DEX treatment induces loss of mitochondrial membrane potential (deltapsim) and cytochrome c release, deltapsim induction does not correlate with thymocyte apoptosis. In fact, while Cyclosporin-A and the caspase-9 inhibitor, Z-LEHD-FMK, inhibit DEX-induced deltapsim, do not influence apoptosis. These data indicate many biochemical events and are activated by DEX treatment of thymocytes and some, but not all, are required for apoptosis.
- Published
- 2003
- Full Text
- View/download PDF
27. Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10.
- Author
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Berrebi D, Bruscoli S, Cohen N, Foussat A, Migliorati G, Bouchet-Delbos L, Maillot MC, Portier A, Couderc J, Galanaud P, Peuchmaur M, Riccardi C, and Emilie D
- Subjects
- Animals, Antigens, CD biosynthesis, Antigens, CD drug effects, B7-1 Antigen biosynthesis, B7-1 Antigen drug effects, B7-2 Antigen, Chemokines biosynthesis, Gene Expression Regulation drug effects, Glucocorticoids pharmacology, Humans, Immune Tolerance, Inflammation immunology, Interleukin-10 pharmacology, Leucine Zippers immunology, Macrophages drug effects, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins drug effects, Mice, Mice, Transgenic, Monocytes drug effects, Monocytes metabolism, NF-kappa B metabolism, Organ Specificity, Receptors, Cell Surface biosynthesis, Receptors, Cell Surface drug effects, Toll-Like Receptor 2, Toll-Like Receptors, Transcription Factors drug effects, Transcription Factors pharmacology, Drosophila Proteins, Macrophages metabolism, Transcription Factors biosynthesis
- Abstract
Glucocorticoids and interleukin 10 (IL-10) prevent macrophage activation. In murine lymphocytes, glucocorticoids induce expression of glucocorticoid-induced leucine zipper (GILZ), which prevents the nuclear factor kappaB (NF-kappaB)-mediated activation of transcription. We investigated whether GILZ could account for the deactivation of macrophages by glucocorticoids and IL-10. We found that GILZ was constitutively produced by macrophages in nonlymphoid tissues of humans and mice. Glucocorticoids and IL-10 stimulated the production of GILZ by macrophages both in vitro and in vivo. Transfection of the macrophagelike cell line THP-1 with the GILZ gene inhibited the expression of CD80 and CD86 and the production of the proinflammatory chemokines regulated on activation normal T-cell expressed and secreted (CCL5) and macrophage inflammatory protein 1alpha (CCL3). It also prevented toll-like receptor 2 production induced by lipopolysaccharide, interferongamma, or an anti-CD40 mAb, as well as NF-kappaB function. In THP-1 cells treated with glucocorticoids or IL-10, GILZ was associated with the p65 subunit of NF-kappaB. Activated macrophages in the granulomas of patients with Crohn disease or tuberculosis do not produce GILZ. In contrast, GILZ production persists in tumor-infiltrating macrophages in Burkitt lymphomas. Therefore, GILZ appears to play a key role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL-10. Glucocorticoid treatment stimulates GILZ production, reproducing an effect of IL-10, a natural anti-inflammatory agent. The development of delayed-type hypersensitivity reactions is associated with the down-regulation of GILZ gene expression within lesions. In contrast, the persistence of GILZ gene expression in macrophages infiltrating Burkitt lymphomas may contribute to the failure of the immune system to reject the tumor.
- Published
- 2003
- Full Text
- View/download PDF
28. Dexamethasone-induced apoptosis of thymocytes: role of glucocorticoid receptor-associated Src kinase and caspase-8 activation.
- Author
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Marchetti MC, Di Marco B, Cifone G, Migliorati G, and Riccardi C
- Subjects
- Animals, Caspase 3, Caspase 8, Caspase 9, Cytochrome c Group metabolism, Enzyme Activation, Enzyme Inhibitors pharmacology, HSP90 Heat-Shock Proteins metabolism, Mice, Mice, Inbred C3H, Phosphatidylinositol Diacylglycerol-Lyase, Phosphoinositide Phospholipase C, Protein Binding, Receptors, Glucocorticoid metabolism, Thyroid Gland drug effects, Type C Phospholipases metabolism, src-Family Kinases metabolism, Apoptosis drug effects, Caspases metabolism, Dexamethasone pharmacology, Thyroid Gland cytology, src-Family Kinases physiology
- Abstract
Glucocorticoid hormones (GCHs) regulate normal and neoplastic lymphocyte development by exerting antiproliferative and/or apoptotic effects. We have previously shown that dexamethasone (DEX)-activated thymocyte apoptosis requires a sequence of events including interaction with the glucocorticoid receptor (GR), phosphatidylinositol-specific phospholipase C (PI-PLC), and acidic sphingomyelinase (aSMase) activation. We analyzed the mechanisms of GCH-activated apoptosis by focusing on GR-associated Src kinase, cytochrome c release, and caspase-8, -9, and -3 activation. We show here that PI-PLC binds to GR-associated Src kinase, as indicated by coimmunoprecipitation experiments. Moreover, DEX treatment induces PI-PLC phosphorylation and activation. DEX-induced PI-PLC phosphorylation, activation, and apoptosis are inhibited by PP1, a Src kinase inhibitor, thus suggesting that Src-mediated PI-PLC activation is involved in DEX-induced apoptosis. Caspase-9, -8, and -3 activation and cytochrome c release can be detected 1 to 2 hours after DEX treatment. Caspase-9 inhibition does not counter cytochrome c release, caspase-8 and caspase-3 activation, and apoptosis. Caspase-8 inhibition counters cytochrome c release, caspase-9 and caspase-3 activation, and apoptosis, thus suggesting that caspase-8 inhibitor can directly inhibit caspase-9 and/or that DEX-induced caspase-8 activation is upstream to mitochondria and can regulate caspase-3 directly or through cytochrome c release and the consequent caspase-9/caspase-3 activation. DEX-induced caspase-8 activation, like ceramide-induced caspase-8 activation, correlates with the formation of Fas-associated death domain protein (FADD)/caspase-8 complex. Caspase-8 activation is countered by the inhibition of macromolecular synthesis and of Src kinase, PI-PLC, and aSMase activation, suggesting it is downstream in the DEX-activated apoptotic pathway of thymocytes.
- Published
- 2003
- Full Text
- View/download PDF
29. Role of GITR in activation response of T lymphocytes.
- Author
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Ronchetti S, Nocentini G, Riccardi C, and Pandolfi PP
- Subjects
- Adjuvants, Immunologic genetics, Adjuvants, Immunologic physiology, Animals, Apoptosis drug effects, CD3 Complex physiology, Glucocorticoid-Induced TNFR-Related Protein, Mice, Mice, Knockout, Receptors, Antigen, T-Cell physiology, Receptors, Nerve Growth Factor genetics, Receptors, Tumor Necrosis Factor genetics, T-Lymphocytes drug effects, T-Lymphocytes physiology, Lymphocyte Activation drug effects, Receptors, Nerve Growth Factor physiology, Receptors, Tumor Necrosis Factor physiology, T-Lymphocytes metabolism
- Abstract
In this study, we describe the generation and characterization of mice in which GITR gene (TNFRSF18 [tumor necrosis factor receptor superfamily 18]), a member of the TNFRSF expressed mainly on T lymphocytes, has been ablated (GITR(-/-) mice). Results indicate that GITR inactivation does not impair the normal development of the lymphoid organs but modulates T-cell activation. In fact, when GITR(-/-) T lymphocytes are activated by treatment with an anti-CD3 monoclonal antibody they proliferate more than wild-type cells. Moreover, activated GITR(-/-) T lymphocytes express higher levels of interleukin-2 receptor, produce larger amounts of interleukin-2, and are more sensitive to activation-induced cell death than controls. These results suggest that GITR is involved in the regulation of T-cell receptor/CD3-driven T-cell activation and programmed cell death.
- Published
- 2002
- Full Text
- View/download PDF
30. Molecular mechanisms of immunomodulatory activity of glucocorticoids.
- Author
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Riccardi C, Bruscoli S, and Migliorati G
- Subjects
- Animals, Cell Survival drug effects, Cytokines biosynthesis, Humans, Receptors, Glucocorticoid drug effects, T-Lymphocytes drug effects, Adjuvants, Immunologic pharmacology, Glucocorticoids pharmacology
- Abstract
The development and function of cells in the immune system are regulated by many intrinsic and extrinsic factors. One class of molecule that affects immune cells belongs to the neuroendocrine system and the best-studied mediators in this category are glucocorticoids. These are small lypophilic molecules that participate in a wide number of normal and pathologic processes. This paper concentrates on their physiologic and pharmacologic effects on the immune response.
- Published
- 2002
- Full Text
- View/download PDF
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