PPARα and PPARγ effectively protect against HIV‐induced inflammatory responses in brain endothelial cells

摘要: Peroxisome proliferator-activated receptors (PPARs) are nuclear which down-regulate inflammatory signaling pathways. Therefore, we hypothesized that alterations of PPAR functions can contribute to human immunodeficiency virus-1 (HIV-1)-induced dysfunction brain endothelial cells. Indeed, treatment with HIV-1 transactivator transcription (Tat) protein decreased transactivation in We next stably over-expressed PPARα and PPARγ a newly developed cell line cells (hCMEC/D3 cells). Tat-induced up-regulation mediators, such as interleukin (IL)-1β, tumor necrosis factor-α, CCL2, E-selectin were markedly attenuated hCMEC/D3 over-expressing or PPARγ. These results confirmed CCL2 promoter activity studies. Similar protective effects observed after activation by exogenous agonists (dPGJ2 rosiglitazone). over-expression also prevented binding factor-κB. Importantly, increased induction IL-1β, co-cultured HIV-1-infected Jurkat The reversed the antagonists (MK886) (GW9662). present data suggest targeting may provide novel therapeutic approach attenuate HIV-1-induced local responses