title: All-trans retinoic acid ameliorates trinitrobenzene sulfonic acid-induced colitis by shifting Th1 to Th2 profile.
abstract: Inflammatory bowel disease is characterized with uncontrolled immune response in inflamed mucosa, with dominance of Th1 cells. Recently, all-trans retinoic acid has been shown that can lead T-cell response by suppressing Th17 development via retinoic acid receptor (RAR), but it is still unknown whether all-trans retinoic acid can modulate Th1 response of inflammatory bowel disease. In the experiment, we investigated the effect of all-trans retinoic acid on trinitrobenzene sulfonic acid (TNBS)-induced murine colitis, and the possible mechanism. Mice were intraperitoneally treated daily with all-trans retinoic acid (the agonist of RAR-alpha) or LE135 (the antagonist of RAR-alpha) or medium, and sacrificed 6 days later. Colon was collected for histological analysis and myeloperoxidase (MPO) activity measurement. Lamina propria mononuclear cells (LPMCs) were isolated, cultured, and assayed for the expressions of T-bet and GATA-3 by the use of Western blot and for cytokine levels by the use of ELISA. All-trans retinoic acid treatment inhibited inflammatory responses as shown by lower histological inflammatory scores and MPO activity, compared with LE135 and medium groups. Furthermore, in LPMCs culture supernatants, the levels of Th1 cytokines (INF-gamma, IL-12, and TNF-alpha) were decreased while those of Th2 cytokines (IL-4 and IL-10) were increased significantly in all-trans retinoic acid-treated mice. In addition, T-bet expression in LPMCs was inhibited and GATA-3 expression was up-regulated in all-trans retinoic acidtreated mice. On the contrary, LE135 showed the reverse effects in colon inflammation and cytokine profile. By shifting Th1 to Th2 profile in inflamed mucosa, all-trans retinoic acid down-regulates inflammatory response and ameliorates acute TNBS-induced colitis, which suggests the ligand of RAR-alpha-based pharmaceutical strategies for managing inflammatory bowel disease.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang City, People's Republic of China. baiap@163.com
authors.forename: Aiping
authors.initials: A
authors.lastname: Bai
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.forename: Pi
authors.initials: P
authors.lastname: Liu
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Peng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003984:Dibenzazepines / Q000008:administration & dosage / Q000494:pharmacology; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D012176:Retinoids / Q000819:agonists* / Q000037:antagonists & inhibitors; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D003984:Dibenzazepines; D050990:GATA3 Transcription Factor; C104182:LE 135; D012176:Retinoids; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014212:Tretinoin; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase