Peripheral LPS administrations up-regulate Fas and FasL on brain microglial cells: a brain protective or pathogenic event?

Abstract

We evaluated the effect of single or repeated intraperitoneal daily LPS injections on expression of Fas/FasL system within the brain. Results obtained, utilizing real-time quantitative RT-PCR, show that, while a bolus injection of LPS robustly increases hippocampal Fas, but not FasL, mRNA expression, repeated LPS administrations also induce FasL up-regulation. Immunofluorescence studies demonstrated, in turn, an increased number of Fas and FasL immunoreactive microglial cells within the brain parenchyma. The increase in FasL immunoreactivity was, in contrast to Fas, still evident 2 weeks following LPS wash-out. At all times, no Fas-positive immunoreactive neurons nor TUNEL-positive resident brain cells were observed. Collectively, these data provide further support for the existence of innate immune responses in brain and, in addition, raise the possibility that Fas and FasL are, within the brain parenchyma, differentially regulated.