Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis.

Abstract

BACKGROUND AND AIMS:

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: Tao Ji, Chao Xu, Lihua Sun, Min Yu, Ke Peng, Yuan Qiu, Weidong Xiao, Hua Yang
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 60 Issue 7 Pg. 1958-66 (Jul 2015) ISSN: 1573-2568 [Electronic] United States
• PMID: 25799939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-formylindolo(3,2-b)carbazole
• Carbazoles
• Interleukin-7
• Receptors, Aryl Hydrocarbon
• Dextran Sulfate

Topics

• Animals
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Carbazoles (pharmacology)
• Cell Line
• Colitis (chemically induced, drug therapy)
• Dextran Sulfate (toxicity)
• Gene Expression Regulation (drug effects, physiology)
• Humans
• Inflammation (metabolism)
• Interleukin-7 (genetics, metabolism)
• Mice
• Receptors, Aryl Hydrocarbon (genetics, metabolism)