The Anti-Hiv Candidate Abx464 Dampens Intestinal Inflammation by Triggering Il-22 Production in Activated Macrophages

Autor: Didier Scherrer, Conception Paul, Karim Chebli, Aude Garcel, Hartmut J. Ehrlich, Jamal Tazi, Laura Papon, Noëlie Campos, Michael Hahne
Přispěvatelé: Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Salvy-Córdoba, Nathalie
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Anti-HIV Agents
medicine.medical_treatment
Science
Anti-Inflammatory Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
Inflammation
Article
Proinflammatory cytokine
Interleukin 22
Mice
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
medicine
Animals
Intestinal Mucosa
Colitis
Multidisciplinary
biology
business.industry
Gene Expression Profiling
Interleukins
Macrophages
Dextran Sulfate
MESH: Anti-HIV Agents/administration & dosage
Anti-Inflammatory Agents/pharmacology
Colitis/drug therapy
Dextran Sulfate/toxicity
Interleukins/metabolism
medicine.disease
Ulcerative colitis
3. Good health
Disease Models
Animal
Treatment Outcome
030104 developmental biology
Cytokine
Immunology
Quinolines
biology.protein
Cytokines
Medicine
Tumor necrosis factor alpha
medicine.symptom
Antibody
business
030215 immunology
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
Scientific Reports
Scientific Reports, Nature Publishing Group, 2017, 7 (1), ⟨10.1038/s41598-017-04071-3⟩
Scientific Reports, 2017, 7 (1), ⟨10.1038/s41598-017-04071-3⟩
ISSN: 2045-2322
Popis: The progression of human immunodeficiency virus (HIV) is associated with mucosal damage in the gastrointestinal (GI) tract. This damage enables bacterial translocation from the gut and leads to subsequent inflammation. Dextran sulfate sodium (DSS-exposure) is an established animal model for experimental colitis that was recently shown to recapitulate the link between GI-tract damage and pathogenic features of SIV infection. The current study tested the protective properties of ABX464, a first-in-class anti-HIV drug candidate currently in phase II clinical trials. ABX464 treatment strongly attenuated DSS-induced colitis in mice and produced a long-term protection against prolonged DSS-exposure after drug cessation. Consistently, ABX464 reduced the colonic production of the inflammatory cytokines IL-6 and TNFα as well as that of the chemoattractant MCP-1. However, RNA profiling analysis revealed the capacity of ABX464 to induce the expression of IL-22, a cytokine involved in colitis tissue repair, both in DSS-treated mice and in LPS-stimulated bone marrow-derived macrophages. Importantly, anti-IL-22 antibodies significantly reduced the protective effect of ABX464 on colitis in DSS-treated mice. Because reduced IL-22 production in the gut mucosa is an established factor of HIV and DSS-induced immunopathogenesis, our data suggest that the anti-inflammatory properties of ABX464 warrant exploration in both HIV and inflammatory ulcerative colitis (UC) disease.
Databáze: OpenAIRE
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