Pioglitazone suppresses the lipopolysaccharide-induced production of inflammatory factors in mouse macrophages by inactivating NF-kappaB.
TZDs (thiazolidinediones) are prescribed as anti-Type II diabetes drugs, but little is known regarding whether TZDs regulate the expression of sPLA2 (secretory phospholipase A2) in macrophages. We have investigated the effects of pioglitazone on LPS (lipopolysaccharide)-induced production of TNF-alpha (tumour necrosis factor alpha), sPLA2-V and -X (groups V and X sPLA2) in RAW 264.7 macrophages. TNF-alpha, sPLA2-V and -X mRNA and protein expression were determined by RT-PCR (reverse transcriptase-PCR) and Western blot analysis, respectively. The activity of NF-kappaB (nuclear factor kappaB) was determined by Western blot and confocal microscopy. LPS induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. Pretreatment with 10 mumol/l pioglitazone significantly suppressed LPS-induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. LPS induced NF-kappaB expression and translocation in the nucleus, but the inductive effects were inhibited by pioglitazone. Our findings indicate that pioglitazone inhibits production of inflammatory factors induced by LPS in murine macrophage cells by inactivating NF-kappaB. Pioglitazone appears to play an anti-inflammatory role in the atherosclerotic process.
Ao
Caihui
C
Department of Cardiology, Peking University First Hospital, Beijing 100034, Peoples Republic of China.
Huo
Yong
Y
Qi
Litong
L
Xiong
Zhuowei
Z
Xue
Lin
L
Qi
Yongfen
Y
D000818:Animals; D002460:Cell Line; D054505:Group V Phospholipases A2 / Q000235:genetics / Q000276:immunology; D054509:Group X Phospholipases A2 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; D000077205:Pioglitazone