HIV-1 GP120-INDUCED APOPTOSIS IN THE RAT NEOCORTEX INVOLVES ENHANCED EXPRESSION OF CYCLOOXYGENASE TYPE-2 (COX-2)

The effect of subchronic intracerebroventricular (i.c.v.) injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein g p120 (100 ng, given daily for up to 7 consecutive days) on cyclo-oxyge nase type 2 (COX-2) expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumi n (100 ng, given i.c.v. for up to 7 days) treated animals (n=6), a sin gle daily injection of the viral protein for 7 consecutive days enhanc ed the number of COX-2 immunoreactive cells in the brain cortex of rat s (n=6 per group) and this was accompanied by a 50% increase over cont rol 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 act ivity, prevented apoptotic death typically produced by gp120 in the ne ocortex of rat suggesting that enhancement of COX-2 expression may be involved in the mechanisms of apoptosis yielded by the HIV-1 coat prot ein. (C) 1998 Academic Press.