[Inhibitory effect of fenofibrate on angiotensin II-induced toll-like receptor 4 expression, myeloperoxidase activity and expression in RAW264.7 cells].
This study is to investigate the effect of fenofibrate on angiotensin II (Ang II)-induced toll-like receptor 4 (TLR4) expression, myeloperoxidase (MPO) activity and expression in murine macrophage line RAW264.7 cells and explore its anti-inflammatory mechanism. TLR4 and MPO mRNA levels were analyzed by RT-PCR, and TLR4 and MPO protein expressions were measured by Western blotting. MPO activity in the cell supernatant was assayed with colorimetry. The results showed that fenofibrate reduced Ang II-induced mRNA and protein expression of TLR4 and inhibited activity, mRNA and protein expression of MPO in RAW264.7 cells in concentration-dependent manner. In addition, TLR4 blocker partially antagonized the effect of Ang II on MPO activity in RAW264.7 cells, and fenofibrate potentiated the inhibitory effect. Meanwhile, fenofibrate significantly suppressed LPS (TLR4 special ligand)-induced MPO activity in RAW264.7 cells. In conclusion, fenofibrate downregulated Ang II-induced TLR4 expression and blocked MPO secretion in RAW264.7 cells via interfering with the TLR4-dependent signaling pathway to alleviate inflammation, which might be one of its novel anti-inflammatory mechanisms.
Ji
Yuan-yuan
YY
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Wang
Zhi-dong
ZD
Liu
Jun-tian
JT
Liu
Na
N
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000960:Hypolipidemic Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D000804:Angiotensin II; D009195:Peroxidase; D011345:Fenofibrate