Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants
Molins, Blanca (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Fuentes-Prior, Pablo (Institut d'Investigació Biomèdica Sant Pau)
Adan Civera, Alfredo (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Antón, Rosa (Institut d'Investigació Biomèdica Sant Pau)
Aróstegui, Juan Ignacio (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Yagüe, Jordi (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Dick, Andrew D. (University College London Institute of Ophthalmology)
Universitat Autònoma de Barcelona

Date:	2016
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.
Grants:	Ministerio de Ciencia e Innovación RD12/0034
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 6 (03 2016) , ISSN 2045-2322

DOI: 10.1038/srep22889
PMID: 26961257

12 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles