PPARalpha and PPARgamma effectively protect against HIV-induced inflammatory responses in brain endothelial cells.

Journal of Neurochemistry
Wen HuangMichal Toborek

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors 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 of brain endothelial cells. Indeed, treatment with HIV-1 transactivator of transcription (Tat) protein decreased PPAR transactivation in brain endothelial cells. We next stably over-expressed PPARalpha and PPARgamma in a newly developed cell line of human brain endothelial cells (hCMEC/D3 cells). Tat-induced up-regulation of inflammatory mediators, such as interleukin (IL)-1beta, tumor necrosis factor-alpha, CCL2, and E-selectin were markedly attenuated in hCMEC/D3 over-expressing PPARalpha or PPARgamma. These results were confirmed in CCL2 and E-selectin promoter activity studies. Similar protective effects were observed in hCMEC/D3 after activation of PPARgamma by exogenous PPAR agonists (dPGJ(2) and rosiglitazone). PPAR over-expression also prevented Tat-induced binding activity and transactivation of nuclear factor-kappaB. Importantly, increased PPAR activity attenuated induction of IL-1beta, tumor necrosis factor-alpha, CCL2, and E-selectin in hCMEC/D3 cells co-...Continue Reading

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Citations

Jun 16, 2009·Neurotoxicity Research·Wenxue LiAvindra Nath
Jan 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wen HuangMichal Toborek
Aug 16, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wen HuangMichal Toborek
Feb 9, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Wen HuangMichal Toborek
Mar 28, 2013·Fluids and Barriers of the CNS·Babette WekslerPierre-Olivier Couraud
Jan 16, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Wen HuangMichal Toborek
Jun 7, 2015·Molecular and Cellular Biochemistry·Wen HuangYanlan Chen
Aug 18, 2017·Critical Reviews in Toxicology·Melissa A DavidsonDaniel Krewski
Mar 4, 2020·Journal of Medicinal Food·Blanca Patricia Lazalde-RamosGabriela Morales-Velazquez
Jun 6, 2018·International Journal of Molecular Sciences·Véronique Ferret-SenaArmando Sena
Sep 10, 2019·Frontiers in Microbiology·Brady L SpencerKelly S Doran
Jul 12, 2020·Fluids and Barriers of the CNS·Amila OmeragicReina Bendayan
Sep 8, 2021·Environmental Science and Pollution Research International·SaiPriyanka Bhimaneni, Anoop Kumar

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