Activation of the aryl hydrocarbon receptor pathway may ameliorate dextran sodium sulfate-induced colitis in mice.
The aryl hydrocarbon receptor (AhR) recognizes numerous small xenobiotic and natural molecules, such as dioxin and natural chemicals, and is involved in the metabolism of these compounds. AhR also has a regulatory role in inflammatory responses. This study investigated whether the activation of the AhR pathway affects dextran sodium sulfate (DSS)-induced colitis, an ulcerative colitis-like model, in mice. DSS-induced colitis was ameliorated by pretreatment with a potent AhR activator, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in mice. In addition, the mice pretreated with TCDD showed increased prostaglandin E2 (PGE2) production in the colon, and inhibition of PGE2 production by indomethacin abrogated the inhibitory effects of TCDD on DSS-induced colitis. Collectively, the activation of the AhR pathway by TCDD may ameliorate DSS-induced colitis, at least in part, through PGE2 production.
Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
Takeyuki
T
Takamura
Daisuke
D
Harama
Shuji
S
Matsuoka
Naomi
N
Shimokawa
Yuki
Y
Nakamura
Ko
K
Okumura
Hideoki
H
Ogawa
Masanori
M
Kitamura
Atsuhito
A
Nakao
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000008:administration & dosage; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D016264:Dextran Sulfate; D019363:Cytochrome P-450 CYP1A1; D015232:Dinoprostone; D007213:Indomethacin