title: Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice.
abstract: We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease.
authors.affiliation: Department of Medicine, The University of Alabama Birmingham, Birmingham, AL 35294, USA.
authors.forename: Tyler T
authors.initials: TT
authors.lastname: Wright
authors.affiliation: Department of Medicine, The University of Alabama Birmingham, Birmingham, AL 35294, USA.
authors.forename: Rachel V
authors.initials: RV
authors.lastname: Jimenez
authors.affiliation: Davis School of Gerontology and Department of Biological Sciences, The University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Davis School of Gerontology and Department of Biological Sciences, The University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Bali
authors.affiliation: Davis School of Gerontology and Department of Biological Sciences, The University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pathology, The University of Alabama Birmingham, Birmingham, AL 35294, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCrory
authors.affiliation: Davis School of Gerontology and Department of Biological Sciences, The University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.affiliation: Department of Medicine, The University of Alabama Birmingham, Birmingham, AL 35294, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai