HIV-1 gp120-induced apoptosis in the rat neocortex involves enhanced expression of cyclo-oxygenase type 2 (COX-2)

The effect of subchronic intracerebroventricular (i.c.v.) injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to 7 consecutive days) on cyclo-oxygenase type 2 (COX-2) expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumin (100 ng, given i.c.v. for up to 7 days) treated animals (n=6), a single daily injection of the viral protein for 7 consecutive days enhanced the number of COX-2 immunoreactive cells in the brain cortex of rats (n=6 per group) and this was accompanied by a 50% increase over control PGE(2) content in whole brain tissue homogenates (n=6). In another series of experiments, pretreatment of rats (n=6) with indomethacin (6.0 mg/kg given i.p. 1 h before gp120 injection), an inhibitor COX activity, prevented apoptotic death typically produced by gp120 in the neocortex of rat suggesting that enhancement of COX-2 expression may be involved in the mechanisms of apoptosis yielded by the HIV-1 coat protein. (C) 1998 Academic Press.