NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions
| Autor: | Coralie Pintard, Pham My-Chan Dang, Jean-Claude Marie, Marjan Mojallali, Philippe Lettéron, Margarita Hurtado-Nedelec, Viviana Marzaioli, Marwa Ben Khemis, Yamina Khichane, Nesrine Makhezer, Aurélie Sannier, Asma Tlili, Jamel El-Benna, Dan Liu, Anne-Laure Pelletier |
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| Přispěvatelé: | Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Hôpital Bichat - Claude Bernard, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Immunology
Inflammation Inflammatory bowel disease [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Lipocalin-2 NOX1 medicine Immunology and Allergy ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences NADPH oxidase Innate immune system biology Chemistry Inflammatory Bowel Disease ROS medicine.disease 3. Good health 030220 oncology & carcinogenesis cardiovascular system biology.protein Cancer research Tumor necrosis factor alpha P22phox medicine.symptom |
| Zdroj: | Mucosal Immunology Mucosal Immunology, Nature Pub. Group, 2019, 12 (1), pp.117-131. ⟨10.1038/s41385-018-0086-4⟩ |
| ISSN: | 1933-0219 1935-3456 |
| DOI: | 10.1038/s41385-018-0086-4⟩ |
| Popis: | Inflammatory bowel disease (IBD) is characterized by severe and recurrent inflammation of the gastrointestinal tract, associated with altered patterns of cytokine synthesis, excessive reactive oxygen species (ROS) production, and high levels of the innate immune protein, lipocalin-2 (LCN-2), in the mucosa. The major source of ROS in intestinal epithelial cells is the NADPH oxidase NOX1, which consists of the transmembrane proteins, NOX1 and p22PHOX, and the cytosolic proteins, NOXO1, NOXA1, and Rac1. Here, we investigated whether NOX1 activation and ROS production induced by key inflammatory cytokines in IBD causally affects LCN-2 production in colonic epithelial cells. We found that the combination of TNFα and IL-17 induced a dramatic upregulation of NOXO1 expression that was dependent on the activation of p38MAPK and JNK1/2, and resulted into an increase of NOX1 activity and ROS production. NOX1-derived ROS drive the expression of LCN-2 by controlling the expression of IκBζ, a master inducer of LCN-2. Furthermore, LCN-2 production and colon damage were decreased in NOX1-deficient mice during TNBS-induced colitis. Finally, analyses of biopsies from patients with Crohn's disease showed increased JNK1/2 activation, and NOXO1 and LCN-2 expression. Therefore, NOX1 might play a key role in mucosal immunity and inflammation by controlling LCN-2 expression. |
| Databáze: | OpenAIRE |
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