[Inhibitory effects of rosiglitazone on angiotensin II-induced toll-like receptor 4 expression and myeloperoxidase activity in RAW264.7 cells].
OBJECTIVE
To investigate the effect of rosiglitazone on angiotensin II (Ang II)-induced mRNA and protein expressions of toll-like receptor 4 (TLR4) and myeloperoxidase (MPO) activity in RAW264.7 cells to explore its anti- inflammatory and anti-atherosclerotic mechanisms.


METHODS
Murine RAW264.7 cells were pretreated with rosiglitazone at 2.5, 5, and 10 micromol/L prior to exposure to AngII (0.1 micromol/L). TLR4 mRNA level was analyzed by RT-PCR, and TLR4 protein expression by Western blotting. MPO activity in the cell supernatant was assayed by colorimetry. In another experiment, the cells were pretreated with a neutralizing anti-TLR4 antibody (1 mg/L) for 1 h prior to rosiglitazone (10 micromol/L) treatment for 1 h, and subsequently stimulated with AngII or LPS (100 micromol/L) for 24 h to observe the change of MPO activity.


RESULTS
Rosiglitazone downregulated AngII-induced mRNA and protein expressions of TLR4, and inhibited MPO activity in RAW264.7 cells in a concentration-dependent manner. The TLR4 blocker partially antagonized the effect of AngII on MPO activity, and the inhibitory effect was markedly enhanced by rosiglitazone. Rosiglitazone significantly inhibited LPS (a specific TLR4 ligand)-induced MPO activity in RAW264.7 cells.


CONCLUSIONS
Rosiglitazone downregulates Ang II-induced TLR4 expression in RAW264.7 cells and inhibits MPO secretion possibly by interfering with TLR4 to relieve the inflammatory reaction, which may be one of its anti-atherosclerotic mechanisms.
Ji
Yuan-yuan
YY
Department of Pharmacology, Xi'an Jiaotong University College of Medicine, Xi'an, China. jiyuanyuan1234@163.com
Wang
Zhi-dong
ZD
Liu
Jun-tian
JT
Liu
Na
N
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D045162:Thiazolidinediones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077154:Rosiglitazone; D000804:Angiotensin II; D009195:Peroxidase