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PPARs Protect Against Tat‐induced Dysfunction of Brain Endothelial Cells
Author(s) -
Huang Wen,
Rha Geun Bae,
Eum Sung Yong,
Andras Ibolya E,
Couraud PierreOlivier,
Hennig Bernhard,
Toborek Michal
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a873-a
Inflammatory responses contribute to HIV Tat‐mediated dysfunction of brain endothelial cells and may participate in the disruption of the blood‐brain barrier in HIV patients. Peroxisome proliferator‐activated receptors (PPARs) are anti‐inflammatory nuclear receptors which can downregulate inflammatory signaling pathways. In the present study, we hypothesize that PPAR‐alpha and PPAR‐gamma can protect against Tat‐induced dysfunction of brain endothelial cells. We generated novel, stably transfected cell lines of human brain endothelial cells (hcMEC) which overexpress PPAR‐alpha or PPAR‐gamma. Treatment with Tat markedly induced mRNA levels of IL‐1beta, TNF‐alpha, MCP‐1, and E‐selectin in normal hcMEC. However, overexpression of PPAR‐alpha or PPAR‐gamma protected against these effects. In addition, Tat‐induced DNA binding activity of NF‐kappaB was attenuated in hcMEC which overexpressed PPAR‐alpha or PPAR‐gamma. The present data suggest that targeting PPAR signaling may provide a novel therapeutic approach to attenuate Tat‐induced dysfunction of brain endothelial cells. Supported by MH63022, MH072567 , and NS39254.