Angiotensin II upregulates Toll-like receptor 4 and enhances lipopolysaccharide-induced CD40 expression in rat peritoneal mesothelial cells

作者：Wu, Jun; Yang, Xiao; Zhang, Yun-Fang; Zhou, Shu-Feng; Zhang, Rui; Dong, Xiu-Qing; Fan, Jin-Jin; Liu, Mei; Yu, Xue-Qing^*

来源：Inflammation Research, 2009, 58(8): 473-482.

DOI：10.1007/s00011-009-0012-z

• Angiotensin II
• Toll-like receptor 4
• NF-kappa B
• CD40
• Rat peritoneal mesothelial cells

Activation of Toll-like receptor 4 (TLR4) in peritoneal mesothelial cells by endotoxin contributes to peritoneal inflammation and fibrosis. Here we investigated TLR4 expression induced by angiotensin II (Ang II) and functional consequences of nuclear factor-kappa B (NF-kappa B) activation and CD40 expression in rat peritoneal mesothelial cells (RPMCs). @@@ TLR4, CD40, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were determined by reverse transcription polymerase chain reaction (RT-PCR) and TLR4, I kappa B alpha, phospho-I kappa B alpha, NF-kappa B p65, and phospho-NF-kappa B p65 were analyzed by Western blot. The intracellular distribution of NF-kappa B p65 was detected by immunofluorescence. @@@ Treatment of RPMCs with Ang II resulted in an increase in the expression of TLR4 mRNA and protein levels. Preincubation of RPMCs with Ang II significantly increased lipopolysaccharide (LPS)-induced phospho-I kappa B alpha and phospho-NF-kappa B p65 protein (P < 0.05 vs. LPS alone) and CD40, TNF-alpha, and IL-6 mRNA levels (P < 0.05 vs. LPS alone). A significantly increased nuclear staining of NF-kappa B p65 in cells treated with Ang II plus LPS was also observed. @@@ Ang II upregulates the expression of TLR4 by RPMCs, resulting in enhanced NF-kappa B signaling and induction of CD40, TNF-alpha, and IL-6 expression. Locally produced Ang II in the peritoneum may have an amplified role in LPS-induced peritoneal inflammation.

• 出版日期2009-8
• 单位中山大学