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Title: | Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants |
Author: | Molins Monteys, Blanca Fuentes Prior, Pablo Adán Civera, Alfredo Antón, Rosa Aróstegui Gorospe, Juan Ignacio Yagüe, Jordi Dick, Andrew D. |
Keywords: | Inflamació Malalties de la retina Degeneració (Patologia) Malalties de les persones grans Inflammation Retinal diseases Degeneration (Pathology) Older people diseases |
Issue Date: | 10-Mar-2016 |
Publisher: | Nature Publishing Group |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/srep22889 |
It is part of: | Scientific Reports, 2016, vol. 6, num. 22889, p. 1-12 |
URI: | http://hdl.handle.net/2445/112425 |
Related resource: | https://doi.org/10.1038/srep22889 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) |
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