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

Immunoelectron microscopy analysis of brain tissue sections and rat-specifi c sandwich ELISA allowed the localization of interleukin-1 beta (IL-1 beta) immunoreactivity in the mitochondria and cytosol of neocortical tissue pre parations from the brain of naive, untreated, rats and rats receiving a sin gle 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. Elev ation of mitochondrial immunoreactive IL-1 beta levels seems to originate f rom the conversion operated by the interleukin converting enzyme (ICE) of m itochondrial pro-IL-1 beta; in fact, IL-1 beta increases reported in the EL ISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1 beta 31-kDa band in conjunction with enhanced expression of the p20 compon ent of activated ICE. In conclusion, the present results demonstrate that g p120-enhanced neocortical expression of IL-1 beta originates, at least in p art, 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 vi ral coat protein in the brain of rats.