关键词: PPAR&gamma, 激动剂, 15d-PGJ2, 趋化因子, 白介素-8, 单核细胞趋化蛋白-1

Abstract:

author: WANGWei-ming(E-mail:wweiming@medmail.com.cn)
ABSTRACT Objective:To investigate the anti-inflammatory actions of PPAR? agonist in LPS-stimulated renal tubular epithelial cells and further to clarify the mechanisms . Methodology: Human renal proximal tubular epithelial (HK-2) cells were divided into four groups: control, LPS (1μg/ml), 15d-PGJ2 (5μM), and 15d-PGJ2 (5μM)+LPS (1μg/ml). The expression of MCP-1 and IL-8 was measured by Real-time PCR and ELISA. To determine whether or not the inhibitory effects of 15d-PGJ2 were PPAR?-dependent RNAi experiments were performed. The location of NF-κB and the IκB phosphorylation was detected by immunofluorescence and western blot methods respectively. Results:The expressions of IL-8 and MCP-1 were increased by 5.67±1.83 and 5.24±1.33 times in mRNA level , 1.62±0.12 and 2.25±0.40 times in protein level respectively. In LPS-stimulated HK-2 cells (p<0.05), and the level of p-IκB in cytoplasm was significantly increased compared with control group. In 15d-PGJ2-pretreated cells, IL-8 and MCP-1 were decreased by 74.2%, 79.4% in mRNA level and 69.0%, 49.4% in protein level compared with LPS group (p<0.05). In pcDNA™6.2 -GW/ EmGFP–mi043-2-1 transfected cells, the levels of IL-8 and MCP-1 still was reduced by 59.2%, 44.1% in mRNA level and 47.1%, 39.4% in protein level in 15d-PGJ2+LPS group compared with LPS group. 15d-PGJ2 was significantly decreased LPS-induced IκB phosphorylation and NF-κB nuclear translocation in pcDNA™6.2 -GW/ EmGFP–mi043-2-1 transfected cells. Conclusions: 15d-PGJ2 inhibits LPS-induced chemokines expression, and are not entirely dependent on PPARγ, which may be related to inhibition of IκB phosphorylation.

Key words: PPAR , agonist, , 15d-PGJ2, chemokine, interleukin-8, monocyte chemoattractant protein-1