PGJ2 antagonizes NF-kappaB-induced HIV-1 LTR activation in colonic epithelial cells.

Intestinal epithelial cells play an important role in early stages of HIV-1 infection and long-term persistence of the virus. Here we determined the mechanism that regulates HIV-1 activation via prostaglandin J(2) (PGJ(2)) in Caco-2 cells. We showed that treatment of Caco-2 cells with PGJ(2) decreased the infectivity of a luciferase reporter virus, pHXB-luc, as well as HIV production following infection of cells with a X4-tropic virus by antagonizing sodium butyrate, a cellular activator known to induce HIV-1 transcription. Transfection of intestinal epithelial cells such as Caco-2, HT-29 and SW620 cells with full-length HIV-1 LTR (pLTR-luc) revealed that PGJ(2) reduced HIV-1 LTR-mediated reporter gene activity. The involvement of NF-kappaB in the PGJ(2)-dependent down-regulation of HIV-1 transcription was further assessed using the kappaB-regulated luciferase-encoding vectors. In Caco-2 cells, PGJ(2) decreased IKK activity, resulting in reduced NF-kappaB translocation to the nucleus. Since sodium butyrate has been associated with a chronic stress response in AIDS patients, our results suggest that addition of PGJ(2) in the environment of infected intestinal epithelial cells could reduce HIV-1 transcription.