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Extracellular cyclophilins in health and disease.

AbstractBACKGROUND:
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.
AuthorsMichael Bukrinsky
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1850 Issue 10 Pg. 2087-95 (Oct 2015) ISSN: 0006-3002 [Print] Netherlands
PMID25445705 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • BSG protein, human
  • Immunosuppressive Agents
  • Basigin
  • Cyclosporine
  • Cyclophilins
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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