Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice.
To investigate the etiological implication of IL-17A in inflammatory bowel disease (IBD), dextran sodium sulfate (DSS) was administered to the mice deficient for the IL-17A gene. They showed only faint manifestations of colitis, as revealed by body weight loss, shrinkage in the colon length, serum haptoglobin concentration, and disease activity index. Although the mortality rate of WT mice reached approximately 60%, more than 90% of the IL-17A KO mice survived the DSS treatment. Histological change was also marginal in the IL-17A KO intestine, in which epithelial damage and inflammatory infiltrates were not obvious and the myeloperoxidase activity elevated only slightly. G-CSF and MCP-1 were abundantly produced in WT mouse intestine, whereas the production of these chemokines was drastically hampered in IL-17A-null intestine. The present results show that IL-17A plays a pivotal role in the pathogenesis of DSS-induced colitis, while MCP-1 and G-CSF may be crucially involved in the IL-17A-induced inflammation.
Ito
Reiko
R
Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kita
Masakazu
M
Shin-Ya
Masaharu
M
Kishida
Tsunao
T
Urano
Atsuyo
A
Takada
Ryusuke
R
Sakagami
Junichi
J
Imanishi
Jiro
J
Iwakura
Yoichiro
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
Kataoka
Keisho
K
Mazda
Osam
O
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics* / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020381:Interleukin-17; D016179:Granulocyte Colony-Stimulating Factor; D016264:Dextran Sulfate