13 results on '"Tamouza H"'
Number of results to display per page
Search Results
2. Renal histopathology
- Author
-
Marie-Lucile, F., primary, Laure-Helene, N., additional, Yosr, C., additional, Anne, M., additional, Fadi, F., additional, Levi, C., additional, Meas-Yedid, V., additional, Daniliuc, C., additional, Karras, A., additional, Olivo-Marin, J. C., additional, Mouthon, L., additional, Guiard, E., additional, Roland, M., additional, Guillevin, L., additional, Jacquot, C., additional, Nochy, D., additional, Thervet, E., additional, Chen, Q., additional, Skerka, C., additional, Uzonyi, B., additional, Lindner, S., additional, Licht, C., additional, Hoppe, B., additional, Riedl, M., additional, Kirschfink, M., additional, Habbich, S., additional, Wolf, G., additional, Strain, L., additional, Goodship, T. H., additional, Zipfel, P. F., additional, Kfoury, H., additional, Alsuwaida, A., additional, Alsaad, K., additional, Alhejaili, F., additional, Alghonaim, M., additional, Alwakeel, J., additional, Husain, S., additional, Aloudah, N., additional, Besso, L., additional, Tamagnone, M., additional, Daidola, G., additional, Burdese, M., additional, Repetto, L., additional, Pasquale, G., additional, Colla, L., additional, Biancone, L., additional, Stratta, P., additional, Segoloni, G. P., additional, Bacalja, J., additional, Bauer Segvic, A. M., additional, Bulimbasic, S., additional, Pacic, A., additional, Knotek, M., additional, Sabljar Matovinovic, M., additional, Galesic, K., additional, Galesic Ljubanovic, D., additional, Zakharova, E., additional, Stolyarevich, E., additional, Vorobjova, O., additional, Tamouza, H., additional, Chemouny, J. M., additional, Flamant, M., additional, Raskova Kafkova, L., additional, Demion, M., additional, Laurent, M., additional, Walker, F., additional, Julian, B. A., additional, Tissandie, E., additional, Tiwari, M. K., additional, Novak, J., additional, Camara, N. O., additional, Benhamou, M., additional, Vrtovsnik, F., additional, Monteiro, R. C., additional, Moura, I. C., additional, Samavat, S., additional, Ahmadpoor, P., additional, Torbati, P., additional, Ghaderi, R., additional, Poorrezagholi, F., additional, Samadian, F., additional, Nafar, M., additional, MII, A., additional, Shimizu, A., additional, Kaneko, T., additional, Yasuda, F., additional, Fukui, M., additional, Masuda, Y., additional, Iino, Y., additional, Katayama, Y., additional, Muller, C., additional, Markovic-Lipkovski, J., additional, Simic-Ogrizovic, S., additional, Naumovic, R., additional, Cirovic, S., additional, Mitrovic, D., additional, Muller, G., additional, Wozniak, A., additional, Janicka-Jedynska, M., additional, Zurawski, J., additional, Kaczmarek, E., additional, Zachwieja, J., additional, Khilji, S., additional, Dorman, T., additional, O'kelly, P., additional, Lampty, L., additional, Leung, K., additional, Shadivan, A., additional, Varghese, C., additional, Walshe, J., additional, Saito, T., additional, Kawano, M., additional, Saeki, T., additional, Mizushima, I., additional, Yamaguchi, Y., additional, Imai, N., additional, Nakashima, H., additional, Umehara, H., additional, Shvetsov, M., additional, Popova, O., additional, Chebotareva, N., additional, Ivanov, A., additional, Bobkova, I., additional, Cremasco, D., additional, Ceol, M., additional, Peruzzi, L., additional, Mazzucco, G., additional, Giuseppina, M., additional, Vezzoli, G., additional, Cristofaro, R., additional, D'angelo, A., additional, Anglani, F., additional, Del Prete, D., additional, Coppolino, G., additional, Comi, N., additional, Bolignano, D., additional, Piraina, V., additional, Talarico, R., additional, Colombo, A., additional, Lucisano, G., additional, Fuiano, G., additional, Bernich, P., additional, Lupo, A., additional, Of Renal Biopsies, T. R., additional, Rastaldi, M. P., additional, Jercan, O. C., additional, Messa, P., additional, Alexandru, D., additional, Mogoanta, L., additional, and Uribe Villegas, V., additional
- Published
- 2012
- Full Text
- View/download PDF
3. IgA Nephropathy and urinary proteomics
- Author
-
Serino, G., primary, Sallustio, F., additional, Cox, S. N., additional, Pesce, F., additional, Schena, F. P., additional, Papista, C., additional, Berthelot, L., additional, Maciel, T. T., additional, Biarnes-Pelicot, M., additional, Tissandie, E., additional, Wang, P. H. M., additional, Tamouza, H., additional, Jamin, A., additional, Bex-Coudrat, J., additional, Gestin, A., additional, Boumediene, A., additional, Arcos-Fajardo, M., additional, England, P., additional, Pillebout, E., additional, Walker, F., additional, Daugas, E., additional, Vrtosvnik, F., additional, Benhamou, M., additional, Cogne, M., additional, Moura, I. C., additional, Monteiro, R. C., additional, Sarcina, C., additional, Tinelli, C., additional, Ferrario, F., additional, Visciano, B., additional, Terraneo, V., additional, Pani, A., additional, Fogazzi, G. B., additional, Furiani, S., additional, Alberghini, E., additional, Buzzi, L., additional, Pozzi, C., additional, Graterol, F., additional, Navarro-Munoz, M., additional, Lopez, D., additional, Ibernon, M., additional, Navarro, M., additional, Troya, M., additional, Perez, V., additional, Sala, N., additional, Serra, A., additional, Bonet, J., additional, Romero, R., additional, Tatematsu, M., additional, Yasuda, Y., additional, Sato, W., additional, Tsuboi, N., additional, Maruyama, S., additional, Imai, E., additional, and Matsuo, S., additional
- Published
- 2012
- Full Text
- View/download PDF
4. Experimental pathology
- Author
-
McCabe, K., primary, Shobeiri, N., additional, Beseau, D., additional, Adams, M., additional, Holden, R., additional, Maio, T., additional, McCabe, K., additional, Laverty, K., additional, Pang, J., additional, Jozefacki, A., additional, Salem, S., additional, Jankowski, V., additional, Passlick-Deetjen, J., additional, Peter, M., additional, Zidek, W., additional, Jankowski, J., additional, Riser, B., additional, Barreto, F., additional, Valaitis, P., additional, Cook, C., additional, White, J., additional, Drueke, T., additional, Holmes, C., additional, Massy, Z., additional, Mizobuchi, M., additional, Ogata, H., additional, Kumata, C., additional, Nakazawa, A., additional, Koiwa, F., additional, Kinugasa, E., additional, Akizawa, T., additional, Lopez, I., additional, Aguilera-Tejero, E., additional, Guerrero, F., additional, Pineda, C., additional, Raya, A. I., additional, Peralta, A., additional, Rodriguez, M., additional, Ciceri, P., additional, Volpi, E., additional, Brenna, I., additional, Brancaccio, D., additional, Cozzolino, M., additional, Bozic, M., additional, deRoij, J., additional, Parisi, E., additional, Ruiz-Ortega, M., additional, Fernandez, E., additional, Valdivielso, J. M., additional, Lee, C.-T., additional, Ng, H.-Y., additional, Tsai, Y.-C., additional, Yang, Y.-K., additional, Niwa, T., additional, Adijiang, A., additional, Shimizu, H., additional, Nishijima, F., additional, Okamoto, T., additional, Kamata, K., additional, Naito, S., additional, Aoyama, T., additional, Tazaki, H., additional, Yamanaka, N., additional, Koenigshausen, E., additional, Ohlsson, S., additional, Woznowski, M., additional, Quack, I., additional, Potthoff, S. A., additional, Rump, L. C., additional, Sellin, L., additional, Maquigussa, E., additional, Pereira, L., additional, Arnoni, C., additional, Boim, M., additional, Lee, K. W., additional, Jeong, J. Y., additional, Jang, W. I., additional, Chung, S., additional, Choi, D. E., additional, Na, K.-R., additional, Shin, Y. T., additional, Slabiak-Blaz, N., additional, Adamczak, M., additional, Ritz, E., additional, Wiecek, A., additional, Uz, E., additional, Uz, B., additional, Sahin Balcik, O., additional, Kaya, A., additional, Akdeniz, D., additional, Bavbek Ruzgaresen, N., additional, Turgut, F. H., additional, Bayrak, R., additional, Carlioglu, A., additional, Akcay, A., additional, Galichon, P., additional, Vittoz, N., additional, Cornaire, E., additional, Baugey, E., additional, Vandermeersch, S., additional, Verpont, M.-C., additional, Mesnard, L., additional, Xu-Dubois, Y.-C., additional, Hertig, A., additional, Rondeau, E., additional, Kokeny, G., additional, Fekeshazy, O., additional, Fang, L., additional, Rosivall, L., additional, Mozes, M. M., additional, Duggan, K., additional, Hodge, G., additional, Ha, H., additional, Chen, J., additional, Lee, L., additional, Tay, C., additional, Macdonald, G., additional, Wang, P. H. M., additional, Tamouza, H., additional, Chemouny, J., additional, Monsinjon, E., additional, Tiwari, M., additional, Vende, F., additional, Vrtovsnik, F., additional, Camara, N. O., additional, Benhamou, M., additional, Monteiro, R. C., additional, Moura, I. C., additional, Rigothier, C., additional, Saleem, M., additional, Ripoche, J., additional, Mathieson, P., additional, Combe, C., additional, Welsh, G., additional, Duwel, A., additional, Munoz-Felix, J. M., additional, Lopez-Novoa, J. M., additional, Martinez-Salgado, C., additional, Koutroutsos, K., additional, Kassimatis, T., additional, Nomikos, A., additional, Giannopoulou, I., additional, Papadakis, J., additional, Nakopoulou, L., additional, Nakamichi, T., additional, Mori, T., additional, Sato, T., additional, Sato, H., additional, Ito, S., additional, Neudecker, S., additional, Heilmann, M., additional, Kramer, P., additional, Wolf, I., additional, Sticht, C., additional, Schock-Kusch, D., additional, Gubhaju, L., additional, Kriz, W., additional, Bertram, J. F., additional, Schad, L. R., additional, Gretz, N., additional, Fuentes-Calvo, I., additional, Kimura, T., additional, Takabatake, Y., additional, Takahashi, A., additional, Kaimori, J.-y., additional, Matsui, I., additional, Namba, T., additional, Kitamura, H., additional, Niimura, F., additional, Matsusaka, T., additional, Soga, T., additional, Rakugi, H., additional, Isaka, Y., additional, Shin, S. J., additional, Kim, K. S., additional, Kim, W. K., additional, Rampanelli, E., additional, Teske, G., additional, Leemans, J., additional, Florquin, S., additional, Small, D., additional, Bennett, N., additional, Roy, S., additional, Gobe, G., additional, Blazquez-Medela, A. M., additional, Garcia-Sanchez, O., additional, Lopez-Hernandez, F. J., additional, Deibel, A., additional, Cheng, J., additional, Warner, G., additional, Knudsen, B., additional, Gray, C., additional, Lien, K., additional, Juskewitch, J., additional, Grande, J., additional, Wang, N., additional, Wang, X., additional, Zeng, M., additional, Sun, B., additional, Xing, C., additional, Zhao, X., additional, Xiong, M., additional, Yang, J., additional, Cao, K., additional, Priante, G., additional, Musacchio, E., additional, Sartori, L., additional, Valvason, C., additional, Baggio, B., additional, Pitlovanciv, E. d. O. N., additional, Reis, L. A., additional, Pessoa, E. A., additional, Teixeira, L., additional, Borges, F. T., additional, Simoes, M. J., additional, Schor, N., additional, Doustar, Y., additional, Mohajeri, D., additional, Smirnov, A. V., additional, Kucher, A. G., additional, Ivanova, G. T., additional, Berseneva, O. N., additional, Parastaeva, M. M., additional, Zarajsky, M. I., additional, Saburova, I. J., additional, Kaukov, I. G., additional, Koppe, L., additional, Fouque, D., additional, Dugenet, Y., additional, Soulage, C., additional, Wan, J., additional, Yang, X., additional, Cui, J., additional, and Zou, Z., additional
- Published
- 2011
- Full Text
- View/download PDF
5. Transferrin Receptor Engagement by Polymeric IgA1 Induces Receptor Expression and Mesangial Cell Proliferation: Role in IgA Nephropathy.
- Author
-
Tamouza, H., Vende, F., Tiwari, M., Arcos-Fajardo, M., Vrtovsnik, F., Benhamou, M., Monteiro, R., and Moura, I.
- Published
- 2007
- Full Text
- View/download PDF
6. Calpains Released by T Lymphocytes Cleave TLR2 To Control IL-17 Expression.
- Author
-
Perez J, Dansou B, Hervé R, Levi C, Tamouza H, Vandermeersch S, Demey-Thomas E, Haymann JP, Zafrani L, Klatzmann D, Boissier MC, Letavernier E, and Baud L
- Subjects
- ATP Binding Cassette Transporter 1 genetics, Animals, Arthritis, Experimental, Cell Line, Cell Proliferation, Gene Expression Regulation, HEK293 Cells, Humans, Inflammation immunology, Inflammation Mediators immunology, Interleukin-17 genetics, Interleukin-2 therapeutic use, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils immunology, RNA Interference, RNA, Small Interfering, Spleen cytology, ATP Binding Cassette Transporter 1 biosynthesis, Calpain metabolism, Interleukin-17 biosynthesis, T-Lymphocytes immunology, Toll-Like Receptor 2 metabolism
- Abstract
Calpains are intracellular proteases that play a key role in inflammation/immunity. Rare studies show that they are partially externalized. However, the mechanism of this secretion and the functions of exteriorized calpains remain poorly understood. In this study, we found that mouse and human lymphocytes secreted calpains through an ABCA1-driven process. In turn, extracellular calpains inhibited IL-17A expression. We were able to attribute this function to a cleavage of the TLR2 extracellular domain, which prevented TLR2-induced transcription of molecules essential for IL-17A induction. Calpain exteriorization and TLR2 cleavage were critical for the control of IL-17A expression by low doses of IL-2. By using newly developed transgenic mice in which extracellular calpains are specifically inactivated, we provide evidence for the relevance of calpain externalization in vivo in regulating IL-17A expression and function in experimental sterile peritonitis and autoimmune arthritis, respectively. Thus, this study identifies calpain exteriorization as a potential target for immune modulation., (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
7. The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy.
- Author
-
Tamouza H, Chemouny JM, Raskova Kafkova L, Berthelot L, Flamant M, Demion M, Mesnard L, Paubelle E, Walker F, Julian BA, Tissandié E, Tiwari MK, Camara NO, Vrtovsnik F, Benhamou M, Novak J, Monteiro RC, and Moura IC
- Subjects
- Adult, Aged, Angiotensin II metabolism, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Antigen-Antibody Complex, Antigens, CD metabolism, Biopsy, Blood Pressure, Calcium metabolism, Cell Proliferation, Cells, Cultured, Enzyme Activation, Female, Glomerulonephritis, IGA enzymology, Glomerulonephritis, IGA pathology, Glomerulonephritis, IGA physiopathology, Humans, Inflammation Mediators metabolism, Interleukin-6 metabolism, Male, Mesangial Cells drug effects, Mesangial Cells enzymology, Mesangial Cells pathology, Middle Aged, Phosphatidylinositol 3-Kinase metabolism, Phosphorylation, Podocytes drug effects, Podocytes enzymology, Podocytes pathology, Proteinuria enzymology, Proteinuria immunology, Proto-Oncogene Proteins c-akt metabolism, Receptors, Transferrin metabolism, Renin-Angiotensin System, TOR Serine-Threonine Kinases metabolism, Time Factors, Young Adult, Cell Communication drug effects, Extracellular Signal-Regulated MAP Kinases metabolism, Glomerulonephritis, IGA immunology, Immunoglobulin A metabolism, MAP Kinase Signaling System drug effects, Mesangial Cells immunology, Podocytes immunology
- Abstract
IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN., Competing Interests: The authors declare no competing financial interests.
- Published
- 2012
- Full Text
- View/download PDF
8. Transglutaminase is essential for IgA nephropathy development acting through IgA receptors.
- Author
-
Berthelot L, Papista C, Maciel TT, Biarnes-Pelicot M, Tissandie E, Wang PH, Tamouza H, Jamin A, Bex-Coudrat J, Gestin A, Boumediene A, Arcos-Fajardo M, England P, Pillebout E, Walker F, Daugas E, Vrtosvnik F, Flamant M, Benhamou M, Cogné M, Moura IC, and Monteiro RC
- Subjects
- Animals, Antigens, CD physiology, Humans, Immunoglobulin A metabolism, Mice, Mice, Inbred C57BL, Protein Glutamine gamma Glutamyltransferase 2, Receptors, Transferrin metabolism, GTP-Binding Proteins physiology, Glomerulonephritis, IGA etiology, Receptors, Fc physiology, Transglutaminases physiology
- Abstract
IgA nephropathy (IgAN) is a common cause of renal failure worldwide. Treatment is limited because of a complex pathogenesis, including unknown factors favoring IgA1 deposition in the glomerular mesangium. IgA receptor abnormalities are implicated, including circulating IgA-soluble CD89 (sCD89) complexes and overexpression of the mesangial IgA1 receptor, TfR1 (transferrin receptor 1). Herein, we show that although mice expressing both human IgA1 and CD89 displayed circulating and mesangial deposits of IgA1-sCD89 complexes resulting in kidney inflammation, hematuria, and proteinuria, mice expressing IgA1 only displayed endocapillary IgA1 deposition but neither mesangial injury nor kidney dysfunction. sCD89 injection into IgA1-expressing mouse recipients induced mesangial IgA1 deposits. sCD89 was also detected in patient and mouse mesangium. IgA1 deposition involved a direct binding of sCD89 to mesangial TfR1 resulting in TfR1 up-regulation. sCD89-TfR1 interaction induced mesangial surface expression of TGase2 (transglutaminase 2), which in turn up-regulated TfR1 expression. In the absence of TGase2, IgA1-sCD89 deposits were dramatically impaired. These data reveal a cooperation between IgA1, sCD89, TfR1, and TGase2 on mesangial cells needed for disease development. They demonstrate that TGase2 is responsible for a pathogenic amplification loop facilitating IgA1-sCD89 deposition and mesangial cell activation, thus identifying TGase2 as a target for therapeutic intervention in this disease.
- Published
- 2012
- Full Text
- View/download PDF
9. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia.
- Author
-
Coulon S, Dussiot M, Grapton D, Maciel TT, Wang PH, Callens C, Tiwari MK, Agarwal S, Fricot A, Vandekerckhove J, Tamouza H, Zermati Y, Ribeil JA, Djedaini K, Oruc Z, Pascal V, Courtois G, Arnulf B, Alyanakian MA, Mayeux P, Leanderson T, Benhamou M, Cogné M, Monteiro RC, Hermine O, and Moura IC
- Subjects
- Animals, Cells, Cultured, Erythroblasts cytology, Erythroblasts drug effects, Erythropoietin pharmacology, Humans, Hypoxia metabolism, Mice, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Mitogen-Activated Protein Kinases metabolism, Phosphatidylinositol 3-Kinases metabolism, Receptors, Transferrin metabolism, Signal Transduction physiology, Transferrin pharmacology, Anemia physiopathology, Cell Proliferation, Erythroblasts physiology, Erythropoiesis physiology, Immunoglobulin A metabolism
- Abstract
Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXXΦ. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
- Published
- 2011
- Full Text
- View/download PDF
10. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia.
- Author
-
Callens C, Coulon S, Naudin J, Radford-Weiss I, Boissel N, Raffoux E, Wang PH, Agarwal S, Tamouza H, Paubelle E, Asnafi V, Ribeil JA, Dessen P, Canioni D, Chandesris O, Rubio MT, Beaumont C, Benhamou M, Dombret H, Macintyre E, Monteiro RC, Moura IC, and Hermine O
- Subjects
- Aged, Animals, Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Antigens, CD immunology, Apoptosis drug effects, Blood Cell Count, CD11b Antigen metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cholecalciferol therapeutic use, Drug Synergism, Female, Gene Expression drug effects, Gene Expression genetics, Gene Expression Profiling, Granulocytes cytology, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells drug effects, Humans, Hydroxycholecalciferols therapeutic use, Iron Chelating Agents therapeutic use, Iron Deficiencies, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, JNK Mitogen-Activated Protein Kinases metabolism, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Lipopolysaccharide Receptors metabolism, Male, Mice, Mice, Nude, Mitogen-Activated Protein Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinases metabolism, Monocytes cytology, Monocytes metabolism, Monocytes pathology, Phosphorylation drug effects, Reactive Oxygen Species metabolism, Receptors, Calcitriol metabolism, Receptors, Transferrin immunology, Xenograft Model Antitumor Assays, Cell Differentiation drug effects, Cholecalciferol pharmacology, Homeostasis drug effects, Iron metabolism, Iron Chelating Agents pharmacology, Leukemia, Myeloid, Acute drug therapy, Receptors, Transferrin antagonists & inhibitors
- Abstract
Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.
- Published
- 2010
- Full Text
- View/download PDF
11. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease.
- Author
-
Matysiak-Budnik T, Moura IC, Arcos-Fajardo M, Lebreton C, Ménard S, Candalh C, Ben-Khalifa K, Dugave C, Tamouza H, van Niel G, Bouhnik Y, Lamarque D, Chaussade S, Malamut G, Cellier C, Cerf-Bensussan N, Monteiro RC, and Heyman M
- Subjects
- Antigens, CD biosynthesis, Biopsy, Chromatography, High Pressure Liquid, Enterocytes metabolism, Glomerulonephritis, IGA diagnosis, Glomerulonephritis, IGA pathology, Humans, Immunoglobulin A chemistry, Immunohistochemistry methods, Models, Biological, Molecular Weight, Receptors, Transferrin biosynthesis, Celiac Disease metabolism, Gliadin chemistry, Immunoglobulin A metabolism, Peptides chemistry, Receptors, Transferrin chemistry
- Abstract
Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA-gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA-gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
- Published
- 2008
- Full Text
- View/download PDF
12. IgA Fc receptor I signals apoptosis through the FcRgamma ITAM and affects tumor growth.
- Author
-
Kanamaru Y, Tamouza H, Pfirsch S, El-Mehdi D, Guérin-Marchand C, Pretolani M, Blank U, and Monteiro RC
- Subjects
- Amino Acid Chloromethyl Ketones pharmacology, Amino Acid Motifs, Animals, Antigens, CD chemistry, Antigens, CD genetics, Caspase 3 metabolism, Cell Line, Tumor, Cells, Cultured, Culture Media, Serum-Free, Cysteine Proteinase Inhibitors pharmacology, Enzyme Activation, Female, Humans, Immunoglobulin A immunology, Immunoglobulin Fab Fragments pharmacology, Inflammation immunology, Inflammation pathology, Leukemia, Basophilic, Acute pathology, Leukemia, Basophilic, Acute therapy, Mast Cells physiology, Mast Cells transplantation, Mice, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Protein Tyrosine Phosphatase, Non-Receptor Type 6 antagonists & inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 6 genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 6 physiology, RNA, Small Interfering pharmacology, Rats, Receptors, Fc chemistry, Receptors, Fc genetics, Receptors, IgG physiology, Recombinant Fusion Proteins physiology, Skin Transplantation, Transfection, Antigens, CD physiology, Apoptosis physiology, Neoplasms pathology, Receptors, Fc physiology
- Abstract
The IgA Fc receptor (FcalphaRI) has dual proinflammatory and anti-inflammatory functions that are transmitted through the immunoreceptor tyrosine-based activation motifs (ITAMs) of the associated FcRgamma subunit. Whereas the involvement of FcalphaRI in inflammation is well documented, little is known of its anti-inflammatory mechanisms. Here we show that monomeric targeting of FcalphaRI by anti-FcalphaRI Fab or serum IgA triggers apoptosis in human monocytes, monocytic cell lines, and FcalphaRI+ transfectants. However, the physiologic ligand IgA induced apoptosis only when cells were cultured in low serum conditions, indicating differences with induction of anti-inflammatory signaling. Apoptosis signaling required the FcRgamma ITAM, as cells transfected with FcalphaRI or with a chimeric FcalphaRI-FcRgamma responded to death-activating signals, whereas cells expressing a mutated FcalphaRI(R209L) unable to associate with FcRgamma, or an ITAM-mutated chimeric FcalphaRI-FcRgamma, did not respond. FcalphaRI-mediated apoptosis signals were blocked by treatment with the pan-caspase inhibitor zVAD-fmk, involved proteolysis of procaspase-3, and correlated negatively with SHP-1 concentration. Anti-FcalphaRI Fab treatment of nude mice injected subcutaneously with FcalphaRI+ mast-cell transfectants prevented tumor development and halted the growth of established tumors. These findings demonstrate that, on monomeric targeting, FcalphaRI functions as an FcRgamma ITAM-dependent apoptotic module that may be fundamental for controlling inflammation and tumor growth.
- Published
- 2007
- Full Text
- View/download PDF
13. Pleiotropic effects of PI-3' kinase/Akt signaling in human hepatoma cell proliferation and drug-induced apoptosis.
- Author
-
Alexia C, Bras M, Fallot G, Vadrot N, Daniel F, Lasfer M, Tamouza H, and Groyer A
- Subjects
- Carcinoma, Hepatocellular pathology, Cell Line, Tumor, DNA Replication drug effects, Doxorubicin pharmacology, G1 Phase, Humans, Insulin-Like Growth Factor I pharmacology, Receptor, IGF Type 1, Apoptosis drug effects, Carcinoma, Hepatocellular enzymology, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction
- Abstract
IGF-II and type I-IGF receptor (IGF-IR) gene expression is increased in primary liver tumors, and transgenic mice overexpressing IGF-II in the liver develop hepatocellular carcinoma (HCC) spontaneously, suggesting that alterations of IGF-IR signaling in vivo may play a role in the auto/paracrine control of hepatocarcinogenesis. We have addressed the contribution of PI-3'K/Akt signaling on the proliferation of HepG2 human hepatoma cells and on their protection against doxorubicin-induced apoptosis. Both basal HepG2 cell DNA replication and that stimulated by IGF-IR signaling were inhibited by the specific PI-3'K inhibitor Ly294002 (Ly). In the former case, PI-3'K signaling overcame cell cycle arrest in G1 via increased cyclin D1 protein and decreased p27kip1 gene expression. Doxorubicin treatment induced apoptosis in HepG2 cells and was concomitant with the proteolytic cleavage of Akt-1 and -2. Drug-induced apoptosis was reversed by IGF-I and this effect was (i) dependent on Akt-1 and -2 phosphorylation and (ii) accompanied by the inhibition of initiator caspase-9 activity, suggesting that IGF-IR signaling interferes with mitochondria-dependent apoptosis. Accordingly, Ly enhanced doxorubicin-induced apoptosis and suppressed its reversal by IGF-I. Altogether, the data emphasize the crucial role of PI-3'K/Akt signaling (i) in basal as well as IGF-IR-stimulated HepG2 cell proliferation and (ii) in controlling both doxorubicin-induced apoptosis (e.g., drug-induced cleavage of Akt) and its reversal by IGF-I (protection against apoptosis parallels the extent of Akt phosphorylation). They suggest that targeting Akt activity or downstream Akt effectors (e.g., GSK3-beta, FOXO transcription factors) may help define novel therapeutic strategies of increased efficacy in the treatment of HCC-bearing patients.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.