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Telmisartan decreases the innate immune response to LPS in circulating human monocytes through PPARγ activation
Author(s) -
Pang Tao,
Benicky Julius,
Wang Juan,
SanchezLemus Enrique,
Saavedra Juan M.
Publication year - 2011
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.25.1_supplement.821.17
Reducing the innate immune response in peripheral monocytes decreases inflammatory allostatic load to the brain and contributes to prevention and treatment of brain disorders. We report that Angiotensin II receptor blocker (ARB) telmisartan is the most potent anti‐inflammatory ARB in cultured human circulating monocytes expressing very few, if any, AT 1 receptors. We investigated whether the anti‐inflammatory effects of telmisartan were related to PPARγ activation. Telmisartan dose‐dependently inhibited LPS‐induced upregulation of pro‐inflammatory factor mRNA expression (TNFα, IL‐6, IL‐1β, COX‐2, ICAM‐1, and MCP‐1), production and release of pro‐inflammatory factors (TNFα, IL‐6, PGE 2 and ROS), phosphorylation of mitogen activated protein (MAP) kinases (ERK, JNK and p38 MAP kinase) and NFκB activation. Telmisartan upregulated the PPARγ target genes CD36 and ABCG1, and its anti‐inflammatory effects were significantly blocked by the selective PPARγ antagonist T0070907 and by PPARγ gene silencing. In addition to its AT 1 receptor blocking activity, telmisartan is an effective anti‐inflammatory compound through PPARγ activation. Telmisartan is a well tolerant compound, widely used for the treatment of high blood pressure in humans. Thus, telmisartan may be an ideal candidate for treatment of brain inflammatory conditions.