Conflict of interests: There are no financial/commercial conflicts of interests.
Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice
Article first published online: 25 JAN 2011
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 26, Issue 2, pages 398–404, February 2011
How to Cite
Yamada, S., Naito, Y., Takagi, T., Mizushima, K., Hirai, Y., Horie, R., Fukumoto, K., Inoue, K., Harusato, A., Yoshida, N., Uchiyama, K., Handa, O., Ishikawa, T., Konishi, H., Wakabayashi, N., Yagi, N., Kokura, S., Kita, M. and Yoshikawa, T. (2011), Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice. Journal of Gastroenterology and Hepatology, 26: 398–404. doi: 10.1111/j.1440-1746.2010.06496.x
- Issue published online: 25 JAN 2011
- Article first published online: 25 JAN 2011
- Accepted manuscript online: 3 SEP 2010 03:13AM EST
- Accepted for publication 24 August 2010.
- non-steroidal anti-inflammatory agents
Background and Aims: The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene.
Methods: Male C57BL/6 (wild-type) and homozygous IL-17A-/- C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines.
Results: The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A-/- mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels.
Conclusion: These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis.