Central nervous system-specific expression of C-reactive protein exacerbates experimental autoimmune encephalomyelitis. (BA3P.202)

Abstract

Abstract Long considered merely a marker of inflammation, new evidence indicates that C-reactive protein (CRP) may also affect the maintenance of health and propagation of disease. Our lab previously showed that human CRP, hepatically synthesized by human CRP transgenic mice (CRPtg), delays onset and reduces severity of Experimental Autoimmune Encephalomyelitis (EAE; a model of Multiple Sclerosis). Though no causal data are available for humans, research suggests that unlike CRPtg, expression/deposition of CRP in the CNS associates with disease, rather than protection. Though human CRP expression in both man and CRPtg mouse is largely hepatic, studies have shown that it is also expressed by multiple cells of the CNS, particularly during neuroinflammation. To test CNS-expressed CRP’s impact on EAE, we made transgenic mice wherein the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) promoter drives human CRP expression. We confirmed that human CRP expression is restricted to the CNS in these neuronal CRPtg (nCRPtg) mice. In contrast to CRPtg, CNS-specific expression of CRP neither delays EAE onset nor improves its symptoms. As in humans, CNS-expressed CRP associates with more severe disease. In summary, observations made with CRPtg vs. nCRPtg reveal a previously unappreciated site-specificity to the impact of CRP on the CNS. The possibility that CRP mediates beneficial vs. detrimental actions depending on the local cellular environment will be investigated.