Accessible Requires Authentication Published by De Gruyter June 2, 2015

C-reactive protein and inflammation: conformational changes affect function

Yi Wu, Lawrence A. Potempa, Driss El Kebir and János G. Filep
From the journal Biological Chemistry

Abstract

The prototypic acute-phase reactant C-reactive protein (CRP) has long been recognized as a useful marker and gauge of inflammation. CRP also plays an important role in host defense against invading pathogens as well as in inflammation. CRP consists of five identical subunits arranged as a cyclic pentamer. CRP exists in at least two conformationally distinct forms, i.e. native pentameric CRP (pCRP) and modified/monomeric CRP (mCRP). These isoforms bind to distinct receptors and lipid rafts, and exhibit distinct functional properties. Dissociation of pCRP into its subunits occurs within the inflammatory microenvironment and newly formed mCRP may then contribute to localizing the inflammatory response. Accumulating evidence indicates that pCRP possesses both pro- and anti-inflammatory actions in a context-dependent manner, whereas mCRP exerts potent pro-inflammatory actions on endothelial cells, endothelial progenitor cells, leukocytes and platelets, and thus may amplify inflammation. Here, we review recent advances that may explain how conformational changes in CRP contribute to shaping the inflammatory response and discuss CRP isomers as potential therapeutic targets to dampen inflammation.


Corresponding author: János G. Filep, Research Center, Maisonneuve-Rosemont Hospital and Department of Pathology and Cell Biology, University of Montréal, 5415 boulevard de l’Assomption, Montréal H1T 2M4, QC, Canada, e-mail:

Acknowledgments

The authors apologize to those whose articles have not been cited due to space limitations. This work was supported by grants from the Canadian Institutes of Health Research (MOP-64283, MOP-94851 and MOP-102619 to J.G.F.) and the National Science Foundation of China-Canadian Institutes of Health Research (CCI-85707 and 30711120578 to Y.W. and J.G.F.).

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Received: 2015-3-30
Accepted: 2015-5-29
Published Online: 2015-6-2
Published in Print: 2015-11-1

©2015 by De Gruyter