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Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance.
J Biol Chem 2014; 289(39):26847-58JB

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+Show Affiliations

From the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.From the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.the Department of Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China.From the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.From the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and.From the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China and xzw63@hotmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25112868

Citation

Zhang, Liya, et al. "Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis By Regulating Th17/Treg Cell Balance." The Journal of Biological Chemistry, vol. 289, no. 39, 2014, pp. 26847-58.
Zhang L, Zhang Y, Zhong W, et al. Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance. J Biol Chem. 2014;289(39):26847-58.
Zhang, L., Zhang, Y., Zhong, W., Di, C., Lin, X., & Xia, Z. (2014). Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance. The Journal of Biological Chemistry, 289(39), pp. 26847-58. doi:10.1074/jbc.M114.590554.
Zhang L, et al. Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis By Regulating Th17/Treg Cell Balance. J Biol Chem. 2014 Sep 26;289(39):26847-58. PubMed PMID: 25112868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance. AU - Zhang,Liya, AU - Zhang,Yanjie, AU - Zhong,Wenwei, AU - Di,Caixia, AU - Lin,Xiaoliang, AU - Xia,Zhenwei, Y1 - 2014/08/11/ PY - 2014/8/13/entrez PY - 2014/8/13/pubmed PY - 2014/12/17/medline KW - Colitis KW - Heme Oxygenase KW - Heme Oxygenase-1 KW - Inflammation KW - Inflammatory Bowel Disease (IBD) KW - T Helper Cells KW - Th17 KW - Treg SP - 26847 EP - 58 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 289 IS - 39 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/25112868/Heme_oxygenase_1_ameliorates_dextran_sulfate_sodium_induced_acute_murine_colitis_by_regulating_Th17/Treg_cell_balance_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=25112868 DB - PRIME DP - Unbound Medicine ER -