Anti-inflammatory Effects of Extracellular Cyclosporins Are Exclusively Mediated by CD147
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- 作者：Miroslav Malesevic ; Danny Gutknecht ; Erik Prell ; Claudia Klein ; Michael Schumann ; Romana A. Nowak ; Jan C. Simon ; Cordelia Schiene-Fischer ; Anja Saalbach
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：September 26, 2013
- 年：2013
- 卷：56
- 期：18
- 页码：7302-7311
- 全文大小：517K
- 年卷期：v.56,no.18(September 26, 2013)
- ISSN：1520-4804
文摘
Leukocyte trafficking and recruitment is a critical process in host immune surveillance and in inflammatory diseases. Extracellular cyclophilins (eCyps) have been identified as a novel class of chemotactic mediators. The impact of eCyp/CD147 interactions for the recruitment of leukocytes during inflammation was analyzed using a structurally simplified cell-impermeable eCyp inhibitor. This compound was highly effective at inhibiting leukocyte migration toward CypA in vitro as well as in the recruitment of leukocytes during inflammation in a mouse model of experimentally induced peritonitis and delayed-type hypersensitivity reaction. By using CD147鈥?鈥?mice in combination with the cell-impermeable eCyp inhibitor, we were able to show that the action of eCyps in inflammation is exclusively mediated by interaction with CD147. Our findings suggest that blocking eCyps may be an effective therapeutic target for reducing inflammatory diseases associated with leukocyte recruitment.