Inhibition of CD200R1 expression by C/EBP beta in reactive microglial cells

Background: in physiological conditions,it is postulated that neurons control microglial reactivity through a series of inhibitory mechanisms,involving either cell contact-dependent,soluble-factor-dependent or neurotransmitter-associated pathways. in the current study,we focus on cd200r1,a microglial receptor involved in one of these cell contact-dependent mechanisms. cd200r1 activation by its ligand,cd200 (mainly expressed by neurons in the central nervous system),is postulated to inhibit the pro-inflammatory phenotype of microglial cells,while alterations in cd200-cd200r1 signalling potentiate this phenotype. little is known about the regulation of cd200r1 expression in microglia or possible alterations in the presence of pro-inflammatory stimuli.methods: murine primary microglial cultures,mixed glial cultures from wild-type and ccaat/enhancer binding protein β (c/ebpβ)-deficient mice,and the bv2 murine cell line overexpressing c/ebpβ were used to study the involvement of c/ebpβ transcription factor in the regulation of cd200r1 expression in response to a proinflammatory stimulus (lipopolysaccharide (lps)). binding of c/ebpβ to the cd200r1 promoter was determined by quantitative chromatin immunoprecipitation (qchip). the involvement of histone deacetylase 1 in the control of cd200r1 expression by c/ebpβ was also determined by co-immunoprecipitation and qchip.results: lps treatment induced a decrease in cd200r1 mrna and protein expression in microglial cells,an effect that was not observed in the absence of c/ebpβ. c/ebpβ overexpression in bv2 cells resulted in a decrease in basal cd200r1 mrna and protein expression. in addition,c/ebpβ binding to the cd200r1 promoter was observed in lps-treated but not in control glial cells,and also in control bv2 cells overexpressing c/ebpβ. finally,we observed that histone deacetylase 1 co-immunoprecipitated with c/ebpβ and showed binding to a c/ebpβ consensus sequence of the cd200r1 promoter in lps-treated glial cells. moreover,histone deacetylase 1 inhibitors reversed the decrease in cd200r1 expression induced by lps treatment.conclusions: cd200r1 expression decreases in microglial cells in the presence of a pro-inflammatory stimulus,an effect that is regulated,at least in part,by c/ebpβ. histone deacetylase 1 may mediate c/ebpβ inhibition of cd200r1 expression,through a direct effect on c/ebpβ transcriptional activity and/or on chromatin structure. © 2012 dentesano et al.; licensee biomed central ltd.