20 results on '"Adriana Delwail"'
Search Results
2. Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis
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Guillaume Larid, Adriana Delwail, Thomas Dalle, Philippe Vasseur, Christine Silvain, Jean-François Jégou, Franck Morel, Jean-Claude Lecron, and Elisabeth Gervais
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Immunology ,Immunology and Allergy - Abstract
ObjectivesPsoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile.MethodsForty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants.ResultsCytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA.ConclusionPsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.
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- 2022
3. Phenotype and cytokine profile in a TRAPS Syndrome family with TNFRSF1A p.(Thr79Met): Association with sacro-iliitis
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Glory Dingulu, Adriana Delwail, Laurence Cuisset, Jean-Claude Lecron, and Elisabeth Gervais
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Rheumatology - Published
- 2022
4. High-Fat Diet–Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis
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Mathilde Pohin, Isabelle Petit-Paris, Jean-Claude Lecron, Hans Yssel, Michel Samson, Laure Favot, Christine Silvain, Franck Morel, Adriana Delwail, Jean-François Jégou, Pierre Levillain, Philippe Vasseur, Laura Serres, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Signalisation et Transports Ioniques Membranaires (STIM), Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomo-Pathologie, CHU de Poiters, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Poitiers, Poitiers University Hospital, Nord Deux-Sevres Hospital, Region Poitou-Charentes, Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,mice ,Erythema ,Fluorescent Antibody Technique ,Dermatitis ,Acanthosis ,Diet, High-Fat ,Real-Time Polymerase Chain Reaction ,Pathology and Forensic Medicine ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,skin inflammation ,Psoriasis ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Psoriasiform Dermatitis ,risk ,[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health ,innate lymphoid-cells ,business.industry ,Interleukin-17 ,il-22 ,Fatty liver ,Flow Cytometry ,medicine.disease ,cytokines ,3. Good health ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Immunology ,liver-disease ,Steatohepatitis ,medicine.symptom ,business - Abstract
International audience; Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermalinfiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1 beta. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients.
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- 2016
5. High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis
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Iris Devaure, Philippe Vasseur, Christine Silvain, Jean-Pierre Tasu, Hanitriniaina Rabeony, Carine Chagneau-Derrode, David Tougeron, Florian Charier, Jean-Claude Lecron, Adriana Delwail, and Jacques Sellier
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Adult ,Male ,Necrosis ,medicine.drug_class ,Pleural effusion ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Infections ,Anti-inflammatory ,Interleukin 22 ,Young Adult ,medicine ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,Hepatology ,Pancreatitis, Acute Necrotizing ,business.industry ,Interleukins ,Gastroenterology ,Middle Aged ,Prognosis ,medicine.disease ,Interleukin-10 ,Pleural Effusion, Malignant ,Interleukin 1 Receptor Antagonist Protein ,Interleukin 10 ,Cytokine ,Acute Disease ,Immunology ,Acute pancreatitis ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,Tomography, X-Ray Computed ,business - Abstract
Pancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection.Consecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 α, IL-1β, TNF- α, IFN-γ, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2.Sixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p = 0.0004).In acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied.
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- 2014
6. Caractérisation du profil cytokinique chez les patients psoriasiques traités par l’adalimumab
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Jean-Claude Lecron, Gérard Guillet, Amandine Buffière Morgado, Jean François Jégou, Adriana Delwail, Laure Favot, and Franck Morel
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Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Dermatology ,business - Abstract
Introduction Un reseau cytokinique complexe a ete decrit dans les lesions cutanees psoriasiques et illustre le role central des cytokines pro-inflammatoires telles que l’IL-23, l’IL-22, l’IL-17, l’IL-1, l’oncostatine M et le TNFα, produites par les cellules immunitaires infiltrees. Recemment, nous avons montre que l’association d’IL-1α, IL-17A, IL-22, OSM et TNFα agit de facon synergique sur les keratinocytes en augmentant l’expression de molecules liees a l’immunite innee et a l’inflammation, telles que des chimiokines et des peptides antimicrobiens, et en inhibant leur programme de differenciation. Ceci genere un modele in vitro d’inflammation cutanee mimant certaines caracteristiques du psoriasis. Nous avons demontre que cette combinaison de cytokines constitue une signature moleculaire des lesions cutanees psoriasiques. En parallele, plusieurs approches therapeutiques anti-cytokine ont ete developpees et le TNFα constitue une cible de choix. Parmi ces traitements, l’adalimumab est une IgG1 monoclonale anti-TNFα entierement humaine qui diminue l’inflammation cutanee et le score de severite clinique d’au moins 75 % chez environ 80 % des patients. Notre objectif etait d’analyser la modification du profil transcriptomique cutane et les concentrations des cytokines circulantes chez les patients psoriasiques pendant le traitement par l’adalimumab. Materiel et methodes Les patients psoriasiques ont ete traites par l’adalimumab. Au bout de 4 et 16 semaines, l’efficacite clinique de la therapie a ete evaluee par les mesures de PASI et de DLQI. Les profils transcriptomiques cutanes avant et apres traitement ont ete determines par RT-PCR quantitative et les cytokines circulantes mesurees par immuno-analyse multiplexe. Resultats Nous observons un effet clair et rapide du traitement par l’adalimumab sur l’expression des cytokines « Th17 », de l’IL-1 et de l’oncostatine M, expliquant les modifications d’expression genique par les keratinocytes (BD2, S100A7, CXCL8, CK10) et la reponse clinique. Une persistance de l’expression des cytokines et de leurs cibles keratinocytaires est egalement observee dans certaines lesions residuelles. En revanche, les concentrations seriques de cytokines sont peu correlees a l’evolution clinique et aux profils d’expression cutanes, ce qui confirme la necessite d’une caracterisation locale des cytokines dans les lesions cutanees. Fait interessant, en plus du maintien de l’expression locale des cytokines chez les patients non repondeurs, un profil cytokinique initial chez les non-repondeurs pourrait suggerer l’identification possible de marqueurs predictifs de resistance/sensibilite au traitement par l’adalimumab. Discussion Nos donnees montrent que le ciblage du TNFα dans le psoriasis a un effet tres large sur le profil d’expression des cytokines Th17 et des marqueurs de l’inflammation de la peau, ce qui explique son efficacite clinique.
- Published
- 2016
7. Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation
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Christine Silvain, Adriana Delwail, Gilles Grateau, Jean-Claude Lecron, Sylvain Normand, B. Massonnet, Laure Favot, Franck Morel, and Laurence Cuisset
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Inflammation ,Mevalonate kinase deficiency ,biology ,medicine.medical_treatment ,Caspase 1 ,Clinical Biochemistry ,Immunology ,Mevalonate kinase ,Familial Mediterranean fever ,medicine.disease ,Disease Models, Animal ,Cytokine ,Mevalonic aciduria ,medicine ,biology.protein ,Animals ,Humans ,Immunology and Allergy ,Mevalonate pathway ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Mevalonate Kinase Deficiency ,Periodic fever syndrome ,Interleukin-1 - Abstract
The mevalonate kinase deficiency (MKD), including hyperimmunoglobulinemia D periodic fever syndrome (HIDS) and the more severe mevalonic aciduria are rare, autosomal recessive, autoinflammatory diseases belonging to the hereditary periodic fever (HPF) family. Other members include: familial mediterranean fever (FMF), the cryopyrin-associated periodic syndromes (CAPS) and TNFR-associated periodic syndromes (TRAPS). MKD is caused by mutations in the gene encoding mevalonate kinase (MK), an enzyme of the cholesterol pathway, leading to its inactivation. The molecular mechanisms linking MKD and abnormalities of isoprenoid biosynthesis to cytokine production and inflammation have yet to be fully elucidated. Statins, which are extensively prescribed for lowering cholesterol, are potent inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, the enzyme directly upstream of MK. In this review, we discuss recent reports demonstrating that in vitro inhibition of the mevalonate pathway by statins specifically increases the production, by activated monocytes, of cytokines of the IL-1 family, by enhancing caspase-1 activity, the enzyme responsible for IL-1beta and IL-18 maturation. The molecular mechanisms involve geranylgeranylation and the enhancement of the activity of G proteins such as Rac-1. Interestingly, activated fibroblasts from MKD patients secrete more IL-1beta than fibroblasts from healthy donors. Taken together, these data highlight the specific enhancement of the IL-1 family of cytokines, the maturation of which is caspase-1-dependent in MKD. Finally, the spectacular decrease in febrile attacks in patients with severe HIDS under IL-1 receptor antagonist (anakinra) treatment, reinforces this hypothesis. Deregulated caspase-1 activation could be responsible for the inflammatory component of MKD, thereby mechanistically linking MKD to FMF and CAPS through cytokines of the IL-1 family.
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- 2009
8. Molecular and functional characterization of a new potassium conductance in mouse ventricular fibroblasts
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Anne Cantereau, Jean-François Faivre, Hamid Moha Ou Maati, Patrick Bois, Adriana Delwail, Jocelyn Bescond, Sophie Demolombe, Najate Benamer, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), INSERM, Centre National de la Recherche Scientifique (CNRS), Cardiopathies et mort subite [ERL 3147], Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, and Fondation de France
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BK channel ,SUR2/Kir6.1 K-channel Cardiac fibroblasts IL-6 Sphingosine-1-phosphate ,Heart Ventricles ,Receptors, Drug ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,030204 cardiovascular system & hematology ,Sulfonylurea Receptors ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,KATP Channels ,Sphingosine ,Glyburide ,medicine ,Animals ,RNA, Messenger ,Sphingosine-1-phosphate ,Potassium Channels, Inwardly Rectifying ,Fibroblast ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,biology ,Interleukin-6 ,Pinacidil ,Fibroblasts ,Molecular biology ,Actins ,Potassium channel ,Cell biology ,Protein Subunits ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Cell culture ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,cardiovascular system ,biology.protein ,Sulfonylurea receptor ,ATP-Binding Cassette Transporters ,Lysophospholipids ,Cardiology and Cardiovascular Medicine ,Ion Channel Gating ,Intracellular - Abstract
(IF : 5,246); International audience; The present work is aimed at identifying and characterizing, at a molecular and functional level, new ionic conductances potentially involved in the excitation–secretion coupling and proliferation of cardiac ventricular fibroblasts. Among potassium channel transcripts which were screened by high-throughput real-time PCR, SUR2 and Kir6.1 mRNAs were found to be the most abundant in ventricular fibroblasts. The corresponding proteins were not detected by western blot following 5 days of cell culture, but had appeared at 7 days, increasing with extended cell culture duration as the fibroblasts differentiated into myofibroblasts. Using the inside-out configuration of the patch-clamp technique, single potassium channels could be recorded. These had properties similar to those reported for SUR2/Kir6.1 channels, i.e. activation by pinacidil, inhibition by glibenclamide and activation by intracellular UDP. As already reported for this molecular signature, they were insensitive to intracellular ATP. In the whole-cell configuration, these channels have been shown to be responsible for a glibenclamide-sensitive macroscopic potassium current which can be activated not only by pinacidil, but also by nanomolar concentrations of the sphingolipid sphingosine- 1-phosphate (S1P). The activation of this current resulted in an increase in cell proliferation and a decrease in IL-6 secretion, suggesting it has a functional role in situations where S1P increases. Overall, this work demonstrates for the first time that SUR2/Kir6.1 channels represent a significant potassium conductance in ventricular fibroblasts which may be activated in physio-pathological conditions and which may impact on fibroblast proliferation and function.
- Published
- 2009
9. L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice
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Bruno Constantin, Régis Hankard, Elise Mok, Christophe Magaud, Frédéric Favreau, Adriana Delwail, Nathalie Neveux, Laboratoire des Adaptations Physiologiques aux Activités Physiques (LAPHAP), Université de Poitiers, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire Ischémie-reperfusion en transplantation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Cytokines et Inflammation, Centre d' investigation clinique-plurithématique du CHU de Poitiers, INSERM, CNRS, AFM, Fonds de la Recherche en Santé Québec, Hôpital Hôtel-Dieu [Paris], Pediatrie Multidisciplinaire - Nutrition de l'Enfant, This work was supported by a grant from Institut National de la Santé et de la Recherche Médicale #33104700 (RAF 01005) (RH) and the Association Française Contre les Myopathies (RH). EM is supported by Les Fonds de la Recherche en Santé Québec PhD Fellowship and Le Prix de Nutrition de la Fédération Association Nationale pour les Traitements A Domicile, les Innovations et la Recherche awarded by La Société Francophone de Nutrition Entérale et Parentérale., and Constantin, Bruno
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Time Factors ,Antioxidant ,[SDV]Life Sciences [q-bio] ,Glutamine ,medicine.medical_treatment ,Duchenne muscular dystrophy ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine.disease_cause ,Antioxidants ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Nuclear factor-kappaB (NF-κB) ,Phosphorylation ,Muscular dystrophy ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Mitogen-Activated Protein Kinase 1 ,0303 health sciences ,Extracellular signal-regulated kinase (ERK1/2 p44/42) ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Mitogen-Activated Protein Kinase 3 ,Glutathione Disulfide ,Age Factors ,NF-kappa B ,Glutamate receptor ,Amino acid, Duchenne muscular dystrophy, Extracellular signal-regulated kinase (ERK1/2 p44/42), Nuclear factor-kappaB (NF-κB), Nutrition, Oxidative stress ,Glutathione ,Amino acid ,3. Good health ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Injections, Intraperitoneal ,medicine.medical_specialty ,MAP Kinase Signaling System ,Down-Regulation ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Muscle, Skeletal ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Nutrition ,030304 developmental biology ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Tumor Necrosis Factor-alpha ,Body Weight ,Skeletal muscle ,medicine.disease ,Mice, Inbred C57BL ,Muscular Dystrophy, Duchenne ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,chemistry ,Dietary Supplements ,Pediatrics, Perinatology and Child Health ,Mice, Inbred mdx ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
International audience; To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. l-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln + Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.
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- 2008
10. Cutting Edge: IL-21 Is a Switch Factor for the Production of IgG1 and IgG3 by Human B Cells
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Jérôme Pène, Sandrine Lécart, Jean-Claude Lecron, Don Foster, Vera Boulay, Paul Guglielmi, Jean-François Gauchat, Elodie Drouet, Adriana Delwail, and Hans Yssel
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Immunoglobulin gamma-Chains ,medicine.medical_treatment ,Antigens, CD19 ,Immunology ,B-Lymphocyte Subsets ,Spleen ,Lymphocyte Activation ,Immunoglobulin E ,Immunoglobulin G ,CD19 ,Cytosine Deaminase ,Antigen ,Cytidine Deaminase ,medicine ,Humans ,Immunology and Allergy ,CD40 Antigens ,Cells, Cultured ,CD40 ,biology ,Immunoglobulin mu-Chains ,Interleukins ,hemic and immune systems ,Cytidine deaminase ,Molecular biology ,Immunoglobulin A ,Immunoglobulin Switch Region ,Immunoglobulin Isotypes ,medicine.anatomical_structure ,Cytokine ,biology.protein ,Cell Division - Abstract
IL-21 is a cytokine that regulates the activation of T and NK cells and promotes the proliferation of B cells activated via CD40. In this study, we show that rIL-21 strongly induces the production of all IgG isotypes by purified CD19+ human spleen or peripheral blood B cells stimulated with anti-CD40 mAb. Moreover, it was found to specifically induce the production of IgG1 and IgG3 by CD40-activated CD19+CD27− naive human B cells. Although stimulation of CD19+ B cells via CD40 alone induced γ1 and γ3 germline transcripts, as well as the expression of activation-induced cytidine deaminase, only stimulation with both anti-CD40 mAb and rIL-21 resulted in the production of Sγ/Sμ switch circular DNA. These results show that IL-21, in addition to promoting growth and differentiation of committed B cells, is a specific switch factor for the production of IgG1 and IgG3.
- Published
- 2004
11. SECRETION OF IL-6, IL-11 AND LIF BY HUMAN CARDIOMYOCYTES IN PRIMARY CULTURE
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Hugues Gascan, Jean-Claude Lecron, Daniel Potreau, John Wijdenes, Pierre Corbi, Cecile Ancey, Adriana Delwail, and Josy Froger
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medicine.medical_specialty ,Time Factors ,Immunology ,Oncostatin M ,Ciliary neurotrophic factor ,Leukemia Inhibitory Factor ,Biochemistry ,Paracrine signalling ,Antigens, CD ,Internal medicine ,Cytokine Receptor gp130 ,medicine ,Humans ,Immunology and Allergy ,Ciliary Neurotrophic Factor ,Autocrine signalling ,Interleukin 6 ,Molecular Biology ,Cells, Cultured ,Aged ,Membrane Glycoproteins ,biology ,Interleukin-6 ,Myocardium ,Proteins ,Interleukin ,Hematology ,Fibroblasts ,Middle Aged ,Interleukin-11 ,Glycoprotein 130 ,Receptors, Interleukin-6 ,Cell biology ,Kinetics ,Endocrinology ,Microscopy, Fluorescence ,biology.protein ,Cytokines ,Peptides ,Leukemia inhibitory factor ,Molecular Chaperones - Abstract
Interleukin (IL)-6-type cytokines are multifunctional proteins involved in cardiac hypertrophy and myocardial protection. Recent studies, performed on animal models, report the production of these cytokines by heart. The aim of this study was to analyse the capacity of myocytes and fibroblasts isolated from human atrium to secrete IL-6, leukaemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and the soluble receptor subunits sIL-6R and sgp130 during primary culture. We detected LIF, IL-11, sgp130 and a large amount of IL-6, but not OSM, CT-1, CNTF nor IL-6R in these culture supernatants. Both cardiomyocytes and fibroblasts are able to spontaneously produce IL-6. The increase of IL-6 production all along the culture period appears to be the consequence of fibroblast proliferation and gp130 stimulation. This is the first demonstration that human cardiac cells are able to secrete IL-6, but also LIF and IL-11 in vitro. These cytokines could be involved in an autocrine and/or a paracrine networks regulating myocardial cyto-protection, hypertrophy and fibrosis.
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- 2002
12. Cyclosporin A inhibition of macrophage colony-stimulating factor (M-CSF) production by activated human T lymphocytes
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Valérie Leprivey-Lorgeot, Jean-Claude Lecron, Stéphanie Frétier, Martine Garcia, John Wijdenes, Vincent Praloran, Arnaud Besse, Adriana Delwail, and Franck Morel
- Subjects
CD4-Positive T-Lymphocytes ,Macrophage colony-stimulating factor ,CD3 Complex ,medicine.medical_treatment ,CD3 ,Immunology ,Anti-Inflammatory Agents ,Biology ,Lymphocyte Activation ,Methylprednisolone ,Cyclosporin a ,medicine ,Humans ,Immunology and Allergy ,Macrophage ,IL-2 receptor ,Macrophage Colony-Stimulating Factor ,Monocyte ,Granulocyte-Macrophage Colony-Stimulating Factor ,CD28 ,Cell Biology ,Molecular biology ,Clone Cells ,medicine.anatomical_structure ,Cytokine ,Depression, Chemical ,Cyclosporine ,biology.protein ,Interleukin-2 ,Interleukin-4 ,Immunosuppressive Agents - Abstract
M-CSF is a pleiotropic cytokine involved in the survival, proliferation, and differentiation of cells of the monocyte/macrophagelineage. M-CSF is produced by numerous cells including CD3-activated Tcells. M-CSF serum levels are increased during acute graft rejection. We tested the in vitro production of M-CSF, GM-CSF, IL-2, and IL-4 byT-cell clones costimulated by CD3 and accessory activation pathways and the effects of cyclosporin A and methylprednisolone. The nine clonesstudied and CD4+ cells purified from peripheral bloodmononuclear cells (PBMC) spontaneously produced low levels of M-CSF, which PMA and CD3 mAb strongly enhanced. In contrast to IL-2, CD28 mAbdid not further enhance this production. CsA inhibited M-CSF productionby clones and purified CD4 T cells. Addition of IL-2, anti IL-2, oranti CD25 mAb to the cultures demonstrated that CsA down-regulatedM-CSF synthesis by activated T cells through its inhibition of IL-2synthesis. These results could help to better understand the complexmechanisms of acute graft rejection and immunosuppression.
- Published
- 2002
13. Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines
- Author
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Adriana Delwail, Joelle Abou-Ghoch, Myrna Medlej-Hashim, Nabiha Salem, André Mégarbané, José-Noel Ibrahim, Jean-Claude Lecron, Eliane Chouery, and Rania Jounblat
- Subjects
Adult ,Lipopolysaccharides ,Male ,medicine.medical_treatment ,Immunology ,Interleukin-1beta ,Familial Mediterranean fever ,Biochemistry ,Peripheral blood mononuclear cell ,Monocytes ,Th2 Cells ,Interleukin-1alpha ,medicine ,Immunology and Allergy ,Humans ,Molecular Biology ,business.industry ,CD28 ,Inflammasome ,Hematology ,Pyrin ,Th1 Cells ,medicine.disease ,Pathophysiology ,Familial Mediterranean Fever ,Cytoskeletal Proteins ,Cytokine ,Case-Control Studies ,Leukocytes, Mononuclear ,Th17 Cells ,Tumor necrosis factor alpha ,Female ,business ,Ex vivo ,medicine.drug ,Acute-Phase Proteins - Abstract
In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines' involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.
- Published
- 2014
14. Circulating soluble gp130, soluble IL-6R, and IL-6 in patients undergoing cardiac surgery, with or without extracorporeal circulation
- Author
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Daniel Potreau, John Wijdenes, Pierre Corbi, Mohammad Rahmati, Jean-Claude Lecron, Paul Menu, and Adriana Delwail
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Extracorporeal Circulation ,medicine.medical_specialty ,Morpholines ,Gastroenterology ,law.invention ,Coronary artery bypass surgery ,law ,Internal medicine ,Cardiopulmonary bypass ,Humans ,Medicine ,Coronary Artery Bypass ,Receptor ,Interleukin 6 ,Aged ,biology ,Interleukin-6 ,business.industry ,Extracorporeal circulation ,General Medicine ,Middle Aged ,Receptors, Interleukin-6 ,Cardiac surgery ,surgical procedures, operative ,medicine.anatomical_structure ,Anesthesia ,biology.protein ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Complication ,circulatory and respiratory physiology ,Artery - Abstract
Objective: Soluble forms of interleukin-6 (IL-6) receptors are known to modulate biological activities of IL-6. The purpose of the study was to measure circulating levels of IL-6, sIL-6R and sgp130 in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB group) or without CPB (non-CPB group). Methods: The CPB group included 19 patients and the non-CPB group 12 patients. Sera levels of IL-6, sIL-6R and sgp130 were measured by specific ELISA at the beginning of the operation (T0, 15 min before skin incision) and 6 h later (T1). Results: IL-6 sera levels were respectively 9 ^ 20 pg/ml (mean ^ SD) and 13 ^ 19 pg/ml at T0 and reached 340 ^ 250 pg/ml and 965 ^ 1060 pg/ml at T1 in CPB and non-CPB groups, indicating a significant increase from T0 to T1, but no differences between the two groups. When compared to T0 values, sgp130 levels decreased in both groups (respectively 105 ^ 37 and 115 ^ 35 ng/ml at T0 for CPB and non-CPB groups, and 72 ^ 25 and 84 ^ 29 ng/ml at T1) while we are not able to detect differences between the groups. Whatever the group or the time, sIL-6R concentrations remained unchanged. Conclusions: We showed that the increase of IL-6 after artery bypass grafting was similar between patients operated with CPB or without CPB. We conclude that the main inductor of IL-6 release is linked to surgical trauma rather than a reaction to CPB. Since it is known that gp130 inhibits IL-6-biological activities, we suggest that the decrease of sgp130 sera levels could further enhance the inflammatory effects of IL-6 in cardiac surgery. q 2000 Elsevier Science B.V. All rights reserved.
- Published
- 2000
15. Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors
- Author
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Cécile Croix, Marie-Claude Viaud-Massuard, David Alagille, Adriana Delwail, Sylvain Normand, Laure Favot, Charlotte Chaulet, Jean-Claude Lecron, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, and Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Down-Regulation ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Pharmacology ,01 natural sciences ,Biochemistry ,Peripheral blood mononuclear cell ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,1H-Imidazo[1 ,5-a]indole-dione ,Drug Discovery ,medicine ,Humans ,Interleukin 6 ,Molecular Biology ,Lenalidomide ,IL-6 ,3-b]pyridine ,biology ,010405 organic chemistry ,Chemistry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Organic Chemistry ,Interleukin ,1H-Pyrrolo-[2 ,Dihydro-thiadiazolo[2 ,3-b]-isoquinolinone-dioxide ,3. Good health ,0104 chemical sciences ,Thalidomide ,Cytokine ,030220 oncology & carcinogenesis ,Drug Design ,biology.protein ,Leukocytes, Mononuclear ,Molecular Medicine ,Tumor necrosis factor alpha ,TNF-alpha ,medicine.drug - Abstract
International audience; Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-alpha and IL-6 production. (C) 2010 Elsevier Ltd. All rights reserved.
- Published
- 2010
16. Pharmacological inhibitors of the mevalonate pathway activate pro-IL-1 processing and IL-1 release by human monocytes
- Author
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Franck Morel, Gilles Grateau, B. Massonnet, Sylvain Normand, Reinhard Moschitz, Nicolas Bourmeyster, Adriana Delwail, Jean-Claude Lecron, Laure Favot, Christine Silvain, Laurence Cuisset, Martine Garcia, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Depatment Biochemical Genetics, Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, tissus épithéliaux et Citokines, Institut de physiologie et biologie cellulaires ( IPBC ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de Médecine interne, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), and Université Pierre et Marie Curie - Paris 6 (UPMC)
- Subjects
Lipopolysaccharides ,rac1 GTP-Binding Protein ,Simvastatin ,peripheral blood mononuclear cell ,medicine.medical_treatment ,Clinical Biochemistry ,Interleukin-1beta ,Farnesyl pyrophosphate ,TNF ,HMGR ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Pharmacology ,p38 Mitogen-Activated Protein Kinases ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,[ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,Immunology and Allergy ,[ SDV.IMM ] Life Sciences [q-bio]/Immunology ,MA ,Hyper IgD and periodic fever syndrome ,Phosphorylation ,0303 health sciences ,Mevalonate kinase deficiency ,biology ,interleukin ,lipopolysaccharide ,Caspase 1 ,HIDS ,GGTI ,hydroxymethylbilane synthase ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,Protein Transport ,Cytokine ,Biochemistry ,HMG-CoA reductase ,FTI ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,lipids (amino acids, peptides, and proteins) ,FPP ,Mevalonate pathway ,Guanosine Triphosphate ,Metabolic Networks and Pathways ,medicine.drug ,phorbol 12-myristate 13-acetate ,LPS ,geranylgeranyl-pyrophosphate ,tumor necrosis factor ,Immunology ,Protein Prenylation ,Mevalonic Acid ,Proinflammatory cytokine ,Cell Line ,03 medical and health sciences ,mevalonate kinase deficiency ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,medicine ,Humans ,MKD ,GGPP ,geranylgeranyltransferase inhibitor ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Protein Precursors ,030304 developmental biology ,PMA ,mAb ,MK ,mevalonate kinase ,PBMC ,[ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Mevalonate kinase ,farnesyltranferase inhibitor ,IL ,mevalonic aciduria ,farnesyl-pyrophosphate ,medicine.disease ,HMBS ,Enzyme Activation ,chemistry ,3-hydroxy-3-methylglutaryl-CoA reductase ,monoclonal antibody ,biology.protein ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Protein Processing, Post-Translational ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030215 immunology ,Interleukin-1 - Abstract
(IF : 2,984); International audience; Objective. The effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase-HMGR-inhibitors) on the inflammatory response remain unclear. HMGR is implicated in the mevalonate pathway, directly upstream of cholesterol biosynthesis. We studied the impairment by this pathway of cytokine production by peripheral blood mononuclear cells (PBMCs) and THP-1 cells. The aim was to identify a specific cytokine "signature" of cells under simvastatin treatment in order to link pharmacological inhibition of the mevalonate pathway and inflammation. Methods. Normal human PBMCs and THP-1 cells were cultured with inhibitors of HMGR (simvastatin), geranylgeranyltransferase (GGTI-298), farnesyltransferase (FTI-277), and/or caspase-1 (Z-VAD(Ome)-FMK). Following culture, cytokine production, caspase-1 activity, IL-1beta mRNA and Rac-1 activity were determined. Results. Pharmacological inhibition of the mevalonate pathway specifically enhanced the release of IL-1alpha, IL-1beta and IL-18 and inhibited IL-1ra production by LPS-activated PBMCs and THP-1 cells. Simvastatin did not modify pro-IL-1beta expression, but enhanced caspase-1 activity, the enzyme responsible for IL-1beta and IL-18 maturation. GGTI-298 also enhanced IL-1-family cytokine production, showing that geranylgeranylation is involved in caspase-1 activation. Additionally, simvastatin enhanced Rac-1 activity. Conclusion. Pharmacological inhibition of the mevalonate pathway by statins highlighted the specific induction of the proinflammatory cytokines of the IL-1 family whose maturation is either directly (i.e. IL-1beta and IL-18), or indirectly (i.e. IL-1alpha) dependant on caspase-1.
- Published
- 2009
17. Stéatohépatite non alcoolique, IL-17A et psoriasis : un ménage à trois délétère ?
- Author
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Adriana Delwail, L. Serres, I. Petit-Paris, Jean-François Jégou, J.-C. Lecron, Christine Silvain, F. Morel, Mathilde Pohin, and Philippe Vasseur
- Subjects
Dermatology - Abstract
La steatopathie hepatique metabolique (SHM), dont la forme inflammatoire correspond a la steatohepatite non alcoolique (NASH), est 2 fois plus frequente dans la population psoriasique ; sa presence pourrait aggraver l’atteinte cutanee. Notre objectif est d’etudier l’impact de la NASH dans un modele murin de psoriasis induit par l’application topique d’imiquimod (IMQ). La NASH est induite par un regime hyperlipidique enrichi en acide cholique de 11 semaines ; de la 9e a la 11e semaine, les souris recoivent tous les 2 jours une application cutanee d’IMQ. Avant induction du psoriasis, les souris recevant le regime hyperlipidique presentent une peau erythemateuse associee a une surexpression cutanee d’IL-17A. Apres traitement par IMQ, l’inflammation cutanee est plus severe chez les souris NASH que chez les souris recevant un regime standard : le score clinique est augmente, l’epaississement epidermique est plus important (62 ± 9 μm vs 90 ± 10 μm, p
- Published
- 2015
18. Role of interleukin-6 in cardiomyocyte/cardiac fibroblast interactions during myocyte hypertrophy and fibroblast proliferation
- Author
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Claire Louault, Jocelyn Bescond, Adriana Delwail, Jean-Claude Lecron, Sandra Fredj, and Daniel Potreau
- Subjects
medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Biology ,Receptor, Angiotensin, Type 1 ,Muscle hypertrophy ,Paracrine signalling ,Mice ,Atrial natriuretic peptide ,Antigens, CD ,Internal medicine ,medicine ,Cytokine Receptor gp130 ,Animals ,Myocytes, Cardiac ,Tissue Distribution ,Autocrine signalling ,Fibroblast ,Cells, Cultured ,Cell Proliferation ,Membrane Glycoproteins ,Interleukin-6 ,Angiotensin II ,Myocardium ,Cardiac myocyte ,Cell Biology ,Hypertrophy ,Fibroblasts ,Losartan ,Endocrinology ,medicine.anatomical_structure ,cardiovascular system ,medicine.drug - Abstract
The process of cardiac hypertrophy is considered to involve two components: that of cardiac myocyte (CM) enlargement and cardiac fibroblast (CF) proliferation. The interleukin-6 (IL-6) family cytokines have been implicated in a variety of cellular and molecular interactions between myocytes and non-myocytes (NCMs), which in turn have important roles in the development of cardiac hypertrophy. In the study of these interactions, we previously detected very high levels of IL-6 in supernatants of a “dedifferentiated model” of adult ventricular CMs cultured with CFs. In the present study, we have used this in vitro coculture system to examine how IL-6 is involved in the interactions between CMs and CFs during CM hypertrophy and CF proliferation. IL-6 and its signal transducer, 130-kDa glycoprotein (gp130), were detected by immunostaining cultured CMs and CFs with anti-IL-6 or anti-gp130 antibodies. Addition of anti-IL-6 or anti-gp130 antagonist antibodies into CM/CF cocultures induced a significant decrease in expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) in CMs. The presence of IL-6 antagonist also resulted in a decrease in the surface area of 12-day-old CMs cultured with CFs or in the presence of fibroblast conditioned medium (FCM), and decreased fibroblast proliferation in CM/CF cocultures, particularly in the presence of a gp130 antagonist. The results also show that angiotensin II (AngII) is mainly secreted by CFs and induces IL-6 secretion in CMs cultured with CFs or with FCM. In addition, the effects of IL-6 on cardiomyocyte hypertrophy and fibroblast proliferation were inhibited by addition of the AT-1 receptor antagonist, losartan. These results suggest that IL-6 contributes significantly to CM hypertrophy by an autocrine pathway and to fibroblast proliferation by a paracrine pathway and that these effects could be mediated by AngII. © 2005 Wiley-Liss, Inc.
- Published
- 2005
19. Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs
- Author
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Adriana Delwail, D. Pariente, Jean-Claude Lecron, Ulrich Meinzer, Tu-Anh Tran, and Yassine Taoufik
- Subjects
Erdheim-Chester Disease ,business.industry ,Immunology ,Treatment outcome ,Interferon-alpha ,Receptors, Interleukin-1 ,Alpha interferon ,Interleukin ,Pharmacology ,medicine.disease ,Antirheumatic Agents ,Interleukin 1 Receptor Antagonist Protein ,Treatment Outcome ,Rheumatology ,Erdheim–Chester disease ,Humans ,Immunology and Allergy ,Medicine ,Female ,Pharmacology (medical) ,Child ,business ,Receptor - Published
- 2011
20. 104 A role for Th17-Derived IL-22 in Psoriatic Skin Inflammation
- Author
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F. Nau, E. Guignouard, Nathalie Pedretti, François-Xavier Bernard, Martine Garcia, H. Yssel, F. Morel, Katia Boniface, Adriana Delwail, G. Dagregorio, Gérard Guillet, and J.-C. Lecron
- Subjects
Interleukin 22 ,Psoriatic skin ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,Inflammation ,Hematology ,medicine.symptom ,business ,Molecular Biology ,Biochemistry - Published
- 2007
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