Human immunodeficiency virus type-1 Tat protein induces nuclear factor (NF)-κB activation and oxidative stress in microglial cultures by independent mechanisms
Article first published online: 7 JUL 2008
Journal of Neurochemistry
Volume 79, Issue 3, pages 713–716, November 2001
How to Cite
Nicolini, A., Ajmone-Cat, M. A., Bernardo, A., Levi, G. and Minghetti, L. (2001), Human immunodeficiency virus type-1 Tat protein induces nuclear factor (NF)-κB activation and oxidative stress in microglial cultures by independent mechanisms. Journal of Neurochemistry, 79: 713–716. doi: 10.1046/j.1471-4159.2001.00568.x
- Issue published online: 7 JUL 2008
- Article first published online: 7 JUL 2008
- Received August 2, 2001; accepted August 7, 2001.
- brain macrophages;
- free radicals;
- nitric oxide;
- tumour necrosis factor-α
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.