p38 Inhibition attenuates the pro-inflammatory response to C-reactive protein by human peripheral blood mononuclear cells

An active role for C-reactive protein (CRP) in inflammatory vascular diseases has been recently suggested. Monocytes play an important role in vascular pathology and are activated by p38 mitogen activated protein kinase (MAPK) dependent mechanisms in many inflammatory settings. Therefore, we investi...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2004-12, Vol.37 (6), p.1111-1114
Main Authors: Lim, Moon Y., Wang, Hui, Kapoun, Ann M., O’Connell, Maile, O’Young, Gilbert, Brauer, Heather Ann, Luedtke, Gregory R., Chakravarty, Sarvajit, Dugar, Sundeep, Schreiner, George S., Protter, Andrew A., Higgins, Linda S.
Format: Article
Language:English
Subjects:
C-reactive protein
C-Reactive Protein - metabolism
Down-Regulation
Humans
Inflammation
Inflammation - metabolism
Leukocytes, Mononuclear - metabolism
Monocytes
p38
Synaptophysin - metabolism
Vascular disease
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Summary:An active role for C-reactive protein (CRP) in inflammatory vascular diseases has been recently suggested. Monocytes play an important role in vascular pathology and are activated by p38 mitogen activated protein kinase (MAPK) dependent mechanisms in many inflammatory settings. Therefore, we investigated whether CRP directly promotes a pro-inflammatory phenotype in human peripheral blood mononuclear cells (HPBMC) via p38 MAPK signaling. CRP exposure leads to a rapid phosphorylation of p38 MAPK in HPBMC. CRP-induced p38 kinase activity in HPBMC was blocked by treatment with an inhibitor of p38 kinase, SD-282. CRP-induced the expression of tissue factor protein and the secretion of IL-6, IL-8, IL-1β, TNFα and PGE 2. Co-exposure to CRP and SD-282 blocked the secretion of these pro-inflammatory and pro-thrombotic mediators. CRP treatment elevated IL-6, IL-8, IL-1β, TNFα, COX-2 and TF mRNA expression. These effects of CRP also required p38 activity, since SD-282 blocked mRNA induction of each. Taken together these data suggest a mechanistic relationship between p38 MAPK signaling and CRP-induced pro-inflammatory and pro-thrombotic activities in HPBMC. Thus, p38 inhibition may represent a novel approach to attenuate inflammation and its consequences in cardiovascular disease.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2004.09.015