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Differential ability of a thiazolidinedione PPARγ agonist to attenuate cytokine secretion in primary microglia and macrophage‐like cells
Author(s) -
Woster Andrew P.,
Combs Colin K.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04706.x
Subject(s) - rosiglitazone , thiazolidinedione , microglia , endocrinology , cytokine , tumor necrosis factor alpha , medicine , inflammation , peroxisome proliferator activated receptor , thp1 cell line , lipopolysaccharide , agonist , secretion , chemistry , receptor , biology , microbiology and biotechnology , cell culture , genetics , type 2 diabetes , diabetes mellitus
Peroxisome proliferator‐activated receptor gamma (PPARγ) agonists are known to inhibit select pro‐inflammatory changes in models of CNS and systemic inflammation. Recent reports suggest that these anti‐inflammatory effects are due to mechanisms other than canonical nuclear receptor‐mediated transcriptional alteration. Using primary microglia and the monocytic cell line, THP‐1, we demonstrate that rosiglitazone, a PPARγ‐activating thiazolidinedione, decreases pro‐inflammatory cytokine secretion as measured by ELISA. Cells were pre‐treated with various thiazolidinediones, including rosiglitazone, prior to stimulation with lipopolysaccharide or phorbol 12‐myristate 13‐acetate (PMA) to stimulate cytokine production. Tumor necrosis factor alpha (TNFα) secretion was significantly inhibited in both primary microglia and THP‐1 cells differentiated for 72 h in the presence of PMA to induce a macrophage‐like phenotype. No reduction in TNFα secretion was observed in undifferentiated THP‐1 cells with rosiglitazone pre‐treatment. Electrophoretic mobility shift assay revealed no significant difference in PPARγ activation between PMA‐differentiated and undifferentiated THP‐1 cells. When PMA‐differentiated and undifferentiated THP‐1 cells were treated with the irreversible PPARγ antagonist, GW 9662, a significant, dose‐dependent decrease in TNFα secretion was observed. These results suggest that the anti‐inflammatory benefit of PPARγ ligands occur independently of classical PPARγ activation.