Palmitate induces interleukin‐8 expression in human aortic vascular smooth muscle cells via Toll‐like receptor 4/nuclear factor‐κB pathway (TLR4/NF‐κB通路介导了软脂酸诱导人主动脉血管平滑肌细胞白细胞介素‐8的基因表达). (1st August 2013)

• Record Type: Journal Article
• Authors: Quan, Jinxing; Liu, Jing; Gao, Xiaobo; Liu, Juxiang; Yang, Haijing; Chen, Wei; Li, Weihua; Li, Yonghong; Yang, Weiguo; Wang, Baoli
• Is Part Of: Journal of diabetes. Volume 6:Number 1(2014:Jan.)
• Page Start: 33
• Page End: 41
• Publication Date: 2013-08-01
• Subjects: Diabetes -- Periodicals; 618.3646005
• DOI: 10.1111/1753-0407.12073
• Languages: English
• ISSNs: 1753-0393

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jdb12073-sec-0001" sec-type="section"> <title>Background</title> <p>Recent evidence demonstrates that saturated free fatty acids (FFAs) induce the inflammatory response via the Toll‐like receptor 4 (TLR4) pathway. Interleukin‐8 (IL‐8) is a proinflammatory cytokine that induces vascular smooth muscle cell proliferation and migration in vitro. However, the regulation of IL‐8 expression by palmitate in human vascular smooth muscle cells (HVSMCs) has not been clarified. The aim of this study was to investigate the regulation of IL‐8 expression by free fatty acids and determine the underlying mechanisms in HVSMCs.</p> </sec> <sec id="jdb12073-sec-0002" sec-type="section"> <title>Methods</title> <p>Human vascular smooth muscle cells were cultured and treated with palmitate, various signaling inhibitors or TLR4 shRNA adenovirus, and the mRNA and protein expression levels of IL‐8, nuclear factor <italic>κ</italic>B (NF‐<italic>κ</italic>B) luciferase activity and NF‐<italic>κ</italic>B p65 binding activity were studied.</p> </sec> <sec id="jdb12073-sec-0003" sec-type="section"> <title>Results</title> <p>Palmitate induced IL‐8 mRNA expression and secretion in a dose‐dependent manner. Palmitate significantly stimulated both nuclear factor <italic>κ</italic>B (NF‐<italic>κ</italic>B) luciferase activity and NF‐<italic>κ</italic>B p65 binding activity, which were markedly diminished by pretreatment with the NF‐<italic>κ</italic>B inhibitor, parthenolide. Parthenolide pretreatment also abolished IL‐8 mRNA and protein induction by palmitate. By contrast, disrupting the ceramide and phosphoinositide‐3 kinase (PI3K) pathways with myriocin and wortmannin did not affect palmitate‐induced IL‐8 expression. Inhibition of protein kinase C (PKC) activation with calphostin C and chelerythrine partially suppressed palmitate‐stimulated IL‐8 expression, but it had no effect on palmitate‐induced NF‐<italic>κ</italic>B activation. Finally, knockdown of TLR4 markedly abolished palmitate‐induced NF‐<italic>κ</italic>B activation and IL‐8 expression.</p> </sec> <sec id="jdb12073-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Palmitate induces IL‐8 gene expression in HVSMCs through the TLR4/NF‐<italic>κ</italic>B pathway.</p> </sec> </abstract>