title: Anti-inflammatory effects of extracellular cyclosporins are exclusively mediated by CD147.
abstract: 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-/- 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.
authors: Max-Planck Research Unit for Enzymology of Protein Folding , Weinbergweg 22, 06120 Halle (Saale), Germany.
authors: Miroslav
authors: M
authors: Malesevic
authors: Danny
authors: D
authors: Gutknecht
authors: Erik
authors: E
authors: Prell
authors: Claudia
authors: C
authors: Klein
authors: Michael
authors: M
authors: Schumann
authors: Romana A
authors: RA
authors: Nowak
authors: Jan C
authors: JC
authors: Simon
authors: Cordelia
authors: C
authors: Schiene-Fischer
authors: Anja
authors: A
authors: Saalbach
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051926:Basigin / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D016572:Cyclosporine / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010539:Permeability
chemical_list: D000893:Anti-Inflammatory Agents; D051926:Basigin; D016572:Cyclosporine; D021983:Cyclophilins