Abstract | BACKGROUND: Extracellular cyclophilins (eCyPs) are pro-inflammatory factors implicated in pathogenesis of a number of inflammatory diseases. Most pathogenic activities of eCyPs are related to their chemotactic action towards leukocytes, which is mediated by eCyP receptor on target cells, CD147, and involves peptidyl-prolyl cis-trans isomerase activity of cyclophilins. This activity is inhibited by cyclosporine A (CsA) and non-immunosuppressive derivatives of this drug. Accumulating evidence for the role of eCyPs in disease pathogenesis stimulated research on the mechanisms of eCyP-initiated events, resulting in identification of multiple signaling pathways, characterization of a variety of effector molecules released from eCyP-treated cells, and synthesis of CsA derivatives specifically blocking eCyPs. However, a number of important questions related to the mode of action of eCyPs remain unanswered. SCOPE OF REVIEW: In this article, we integrate available information on release and function of extracellular cyclophilins into a unified model, focusing on outstanding issues that need to be clarified. MAJOR CONCLUSIONS: Extracellular cyclophilins are critical players in pathogenesis of a number of inflammatory diseases. Their mechanism of action involves interaction with the receptor, CD147, and initiation of a poorly characterized signal transduction process culminating in chemotaxis and production of pro-inflammatory factors. GENERAL SIGNIFICANCE: Extracellular cyclophilins present an attractive target for therapeutic interventions that can be used to alleviate symptoms and consequences of acute and chronic inflammation. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.
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Authors | Michael Bukrinsky |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1850
Issue 10
Pg. 2087-95
(Oct 2015)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 25445705
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- BSG protein, human
- Immunosuppressive Agents
- Basigin
- Cyclosporine
- Cyclophilins
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Topics |
- Animals
- Basigin
(genetics, metabolism)
- Cyclophilins
(genetics, metabolism)
- Cyclosporine
(pharmacology)
- Humans
- Immunosuppressive Agents
(pharmacology)
- Inflammation
(genetics, metabolism, pathology, therapy)
- Signal Transduction
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