C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor α, on human monocytes

Didier Hanriot; Gaëlle Bello; Armelle Ropars; Carole Seguin-Devaux; Gaël Poitevin; Sandrine Grosjean; Vèronique Latger-Cannard; Yvan Devaux; Faiez Zannad; Vèronique Regnault; Patrick Lacolley; Paul-Michel Mertes; Ketsia Hess; Dan Longrois

doi:10.1160/TH07-06-0410

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(03): 558-569
DOI: 10.1160/TH07-06-0410

Platelets and Blood Cells

Schattauer GmbH

C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor α, on human monocytes

Didier Hanriot^*

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Gaëlle Bello^*

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Armelle Ropars

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Carole Seguin-Devaux

⁵CRP-Sante, Luxembourg Hospital, Luxembourg

,

Gaël Poitevin

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Sandrine Grosjean

³CHU Nancy, Nancy, France

,

Vèronique Latger-Cannard

²Henri Poincarè University, Nancy, France

³CHU Nancy, Nancy, France

⁴INSERM, U734, Nancy, France

,

Yvan Devaux

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

⁵CRP-Sante, Luxembourg Hospital, Luxembourg

,

Faiez Zannad

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Vèronique Regnault

²Henri Poincarè University, Nancy, France

⁴INSERM, U734, Nancy, France

,

Patrick Lacolley

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Paul-Michel Mertes

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Ketsia Hess^*

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

,

Dan Longrois^*

¹INSERM, U684, Nancy, France

²Henri Poincarè University, Nancy, France

› Author Affiliations

Abstract

Summary

Non-specific markers of inflammation such as C-reactive protein (CRP) are associated statistically with an increased risk of atherosclerosis through mechanisms that have not yet been fully elucidated.We investigated the effects of CRP on several aspects of human monocyte biology, a cell type involved in the initiation and progression of atherosclerosis. Blood monocytes isolated from healthy men and premenopausal women (n=9/group) were exposed to purified CRP (25 μg/ml) for 12 hours. Changes in gene expression were analyzed using a custom-made array containing oligonucleotide sequences of 250 genes expressed by activated monocytes and confirmed by quantitative PCR. CRP increased significantly the expression of the cytokines interleukin (IL)-1α, IL-1β and IL-6, and the chemokines GRO-α, GRO-β and IL-8. CRP also displayed anti-inflammatory effects through upregulation of liver X receptor (LXR) α and activin receptor expression, and down-regulation of alpha 2-macroglobulin expression. Increased LXRα mRNA expression in both monocytes and the monocytic cell lineTHP-1 was associated with increased LXRα protein expression and nuclear translocation, as well as increased ABCA1 mRNA expression, a target gene of LXRα. Western Blot analysis revealed CRP-induced nuclear translocation of NF-κB and activation of p42/44, MAP and Akt kinases. CRP-induced LXRá mRNA expression was inhibited by anti-CD64 (FcγRI) antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating study demonstrates that CRP modulates the expression of genes that contribute to both pro- and anti-inflammatory responses in human monocytes. Among these novel anti-inflammatory effects, we show clearly that CRP activates the LXRα pathway.

Keywords

Atherosclerosis - inflammation - C-reactive protein - liver X receptors - microarrays

Full Text

References

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