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

Blanca Molins, Pablo Fuentes-Prior, Alfredo Adán, Rosa Antón, Juan I. Arostegui, Jordi Yagüe, Andrew D. Dick

    Research output: Contribution to journalArticleResearchpeer-review

    30 Citations (Scopus)

    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.
    Original languageEnglish
    Article number22889
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 10 Mar 2016

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