Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Abstract Background Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of evolutionarily conserved family small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet exact in neuroinflammation poorly understood. In order shed light mechanism inflammation modulation by HSPB1, we investigated effect HSPB1 neuroinflammatory processes an vivo vitro model acute brain injury. Methods this study, used transgenic mouse strain overexpressing human protein. experiments, 7-day-old wild-type mice were treated with ethanol. Apoptotic cells detected using TUNEL assay. The mRNA levels cytokines glial cell markers examined RT-PCR immunohistochemistry brain. We also established primary neuronal, astrocyte, microglial cultures which subjected cytokine ethanol treatments. TNFα hHSPB1 measured from supernates ELISA, intracellular expression was analyzed fluorescent immunohistochemistry. Results Following treatment, brains hHSPB1-overexpressing showed significantly higher level pro-inflammatory ( Tnf , Il1b ), microglia Cd68 Arg1 astrocyte Gfap ) compared brains. Microglial activation, 1 week later, reactive astrogliosis certain areas ethanol-treated those wild-types. Despite remarkably high pro-apoptotic did not exhibit apoptosis. Our data suggest that hHSPB1, showing highest astrocytes, responsible for inflammation-regulating effects. Microglia main source our model. isolated release under inflammatory conditions. Conclusions work provides novel evidence overexpression regulating intensifying enhancing but increasing neuronal These results may play complex ethanol-induced response.