title: Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance.
abstract: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium-induced model of experimental murine colitis. BALB/c mice were administered 4% dextran sulfate sodium orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX. The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down-regulates retinoic acid-related orphan receptor γt expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD.
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.
authors.forename: Caixia
authors.initials: C
authors.lastname: Di
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and. Electronic address: xzw63@hotmail.com.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000494:pharmacology*; D006427:Hemin / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D008565:Membrane Proteins; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D016753:Interleukin-10; D006427:Hemin; D016264:Dextran Sulfate; C028025:protoporphyrin IX; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Colitis; Heme Oxygenase; Heme Oxygenase-1; Inflammation; Inflammatory Bowel Disease (IBD); T Helper Cells; Th17; Treg
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