title: All-trans retinoic acid attenuates experimental colitis through inhibition of NF-κB signaling.
abstract: Inflammatory bowel disease (IBD) is characterized by excessive innate immune cell activation, which is responsible for tissue damage and induction of adaptive immune responses. All-trans retinoic acid (ATRA), the ligand of retinoic acid receptors (RAR), has been previously shown to regulate adaptive immune responses and restore Th17/Treg balance, while its role in regulation of innate immune cell function such as macrophages remains to be elucidated. The study was performed to explore the effect of ATRA on regulation of innate immune responses during dextran sulfate sodium (DSS) induced murine colitis. The mice with DSS colitis were administered with vehicle, ATRA, or LE135. Colitis was evaluated by clinical symptoms, tissue myeloperoxidase (MPO) activity, and the expressions of CD68 and nuclear factor (NF) κB p65, and tumor necrosis factor (TNF) level in inflamed colon. RAW 264.7 cells were pretreated with vehicle, ATRA, or LE135, followed by LPS challenge in vitro. ATRA administration ameliorates DSS-induced colitis evidenced with decreased TNF level and CD68 expression, while LE135 leads to exacerbation of colitis. ATRA treatment in vitro dampens LPS induced NF-κB activation and TNF production of RAW 264.7 cells. Together, our data show a crucial role of ATRA in the progress of acute colitis through inhibiting NF-κB activation, and suggest that ATRA represents a novel therapeutic approach for the management of IBD.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hong
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. Electronic address: baiap@163.com.
authors.forename: Aiping
authors.initials: A
authors.lastname: Bai
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016264:Dextran Sulfate; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009195:Peroxidase; D014212:Tretinoin; D048069:Tumor Necrosis Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: All-trans retinoic acid; Colitis; Macrophage; NF-κB; RAR