Human immunodeficiency virus type-1 Tat protein induces nuclear factor (NF)-κB activation and oxidative stress in microglial cultures by independent mechanisms

Abstract

We have extended our previous findings and shown that human immunodeficiency virus Tat protein, in addition to nitric oxide (NO), stimulated rat microglial cultures to release pro-inflammatory cytokine interleukin-1β and tumour necrosis factor-α in a nuclear factor (NF)-κB-dependent manner. At the same time, Tat stimulated the accumulation of free radicals, as indicated by the increased levels of isoprostane 8-epi-prostaglandin F2α (8-epi-PGF2α), a reliable marker of lipid peroxidation and oxidative stress, by a mechanism unrelated to NF-κB activation. The presence of free radical scavengers abrogated Tat-induced 8-epi-PGF2α, accumulation without affecting NO and cytokine production. Consistently, Tat-induced IκBα degradation - an index of NF-κB activation - was not affected by free radical scavengers, but was prevented by an NF-κB-specific inhibitor. Our observations indicate that NF-κB plays a key role in Tat-dependent microglial activation, and that oxidative stress and NF-κB activation induced by Tat occur by independent mechanisms.