Evidence that increases of mitochondrial immunoreactive IL-1β by HIV-1 gp120 implicate in situ cleavage of pro-IL-1β in the neocortex of rat

Immunoelectron microscopy analysis of brain tissue sections and rat-specific sandwich ELISA allowed the localization of interleukin-1 beta (IL-1 beta) immunoreactivity in the mitochondria and cytosol of neocortical tissue preparations from the brain of naive, untreated, rats and rats receiving a single daily injection into one lateral cerebral ventricle (i.c.v.) of bovine serum albumin (BSA; 100 ng/day) for seven consecutive days. Interestingly, seven days i.c.v. treatment with the HIV-1 coat protein gp120 (100 ng/day) enhances IL-1 beta immunoreactivity in the cellular fractions studied. Elevation of mitochondrial immunoreactive IL-1 beta levels seems to originate from the conversion operated by the interleukin converting enzyme (ICE) of mitochondrial pro-IL-1 beta; in fact, IL-1 beta increases reported in the ELISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1 beta 31-kDa band in conjunction with enhanced expression of the p20 component of activated ICE. In conclusion, the present results demonstrate that gp120-enhanced neocortical expression of IL-1 beta originates, at least in part, from in situ cleavage of mitochondrial pro-IL-1 beta and suggest that this, together with the central role of the mitochondrion in the expression of programmed cell death, may be important for apoptosis induced by the viral coat protein in the brain of rats.