title: Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis.
abstract: OBJECTIVE
  The pathogenesis of inflammatory bowel disease (IBD) is associated with dysregulation of intestinal immune system. Aryl hydrocarbon receptor (AHR) is believed to control the chronic inflammation in the gut. Besides, interleukin-7 (IL-7) is proved to be an important cytokine that activates mucosal inflammation in IBD. Moreover, intraepithelial lymphocytes (IELs) are one of the key immunological compartments involved in regulating intestinal inflammation. In this study, we investigated the function of 6-formylindolo (3,2-b) carbazole (Ficz), a ligand of AHR, on IL-7, colitis, and IEL phenotypes.
  
  
  METHODS
  Colitis was induced by administration of dextran sulfate sodium (DSS) to wild-type C57BL/6J mice for 7 days. Mice were weighted, colon tissues were collected and measured, and histology analyses were performed. IELs were isolated from colon, and the phenotype and activation of IELs were examined using flow cytometry detection. The expression of AHR and IL-7 was measured by immunofluorescence, Western blot, and RT-PCR.
  
  
  RESULTS
  Ficz down-regulated epithelial-derived IL-7 expression in mice with DSS-induced colitis and ameliorated DSS-induced colitis. Ficz also decreased CD8αβ(+) and CD8(+) IEL subpopulations, enhanced TCRγδ(+) IEL subpopulation, and reduced the percentage of activated CD4(+) and CD8(+) subpopulations.
  
  
  CONCLUSIONS
  Ficz could down-regulate epithelial-derived IL-7 expression in mice with DSS-induced colitis and inhibit inflammation in the gastrointestinal tract of mice. AHR-related compounds might be the new and promising therapeutic medicaments for the treatment of patients with IBD.
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors: Tao
authors: T
authors: Ji
authors: Chao
authors: C
authors: Xu
authors: Lihua
authors: L
authors: Sun
authors: Min
authors: M
authors: Yu
authors: Ke
authors: K
authors: Peng
authors: Yuan
authors: Y
authors: Qiu
authors: Weidong
authors: W
authors: Xiao
authors: Hua
authors: H
authors: Yang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy; D016264:Dextran Sulfate / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: C111855:6-formylindolo(3,2-b)carbazole; D002227:Carbazoles; D015851:Interleukin-7; D018336:Receptors, Aryl Hydrocarbon; D016264:Dextran Sulfate