Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants.

Abstract

Inflammation and immune-mediated processes are pivotal to the pathogenic progression of age-related macular degeneration (AMD). Although plasma levels of C-reactive protein (CRP) have been shown to be associated with an increased risk for AMD, the pathophysiological importance of the prototypical acute-phase reactant in the etiology of the disease is unknown, and data regarding the exact role of CRP in ocular inflammation are limited. In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the "risk" His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained.

• Authors: Blanca Molins, Pablo Fuentes-Prior, Alfredo Adán, Rosa Antón, Juan I Arostegui, Jordi Yagüe, Andrew D Dick
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 22889 (Mar 10 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26961257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-8
• Complement Factor H
• C-Reactive Protein

Topics

• Aged
• C-Reactive Protein (metabolism)
• Cell Line
• Chemotaxis, Leukocyte
• Complement Factor H (chemistry, genetics, metabolism)
• Cytokines (metabolism)
• Down-Regulation
• Female
• Genetic Predisposition to Disease
• Humans
• Inflammation (metabolism)
• Interleukin-8 (metabolism)
• Leukocytes, Mononuclear (physiology)
• Male
• Polymorphism, Genetic
• Protein Binding
• Protein Multimerization
• Retinal Pigment Epithelium (metabolism)
• Wet Macular Degeneration (genetics, metabolism)