Rosiglitazone down-regulates lipopolysaccharide-induced expression of CD40 and intercellular adhesion molecule 1 in rat peritoneal mesothelial cells through a NF-κB dependent mechanism / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effect and mechanism by which PPARγ ligand, rosiglitasone, regulates the expression of CD40 and intercellular adhesion molecule 1 (ICAM-1) in the rat peritoneal mesothelial cells (RPMCs) induced by lipopolysaccharide (LPS). Methods RPMCs were harvested from Sprague-Dawley rat peritoneal cavity and maintained under defined in vitro conditions. The cells were randomly divided into groups as follows medium, LPS (5 mg/L), LPS (5 mg/L)+BAY11-7085(5 μmol/L, NF-κB inhibitor), rosiglitazone (10 μmol/L or 20 μmol/L, peroxisome proliferator-activated receptor γ activator), LPS (5 mg/L)+rosiglitazone (10 μmol/L)+GW9662 (3 μmol/L, peroxisome proliferator-aetivatcd receptor γ antagonist), and LPS (5 mg/L)+vehicle (DMSO 0.2 ml/L). The expressions of CD40 and ICAM-1 RNA in RPMCs were examined by RT-PCR after 3 hour treatment, and the protein expressions of CD40, ICAM-1, p-NF-κB p65 and p-IκBα were examined by Western blot or immunofluorescence after 24 hour treatment. Results Following treatment with LPS, both the expressions of CD40 and ICAM-1 protein in RPMCs were up-regulated significantly (P<0.05), and the phosphoralation of p65 was increased greatly (1.10±0.17 vs 0.55±0.06, P<0.05). BAY11-7085 (5 μmol/L) significantly decreased the protein expression of p-p65 (0.22±0.11 vs 1.10±0.17, P<0.01), CD40 (0.34±0.02 vs 0.50±0.06, P<0.05) and ICAM-1 (0.35±0.16 vs 0.74±0.03, P<0.05). Pretreated with rosiglitazone for 3 h then added with LPS for 1 h, the levels of p-p65, CD40 and ICAM-1 in RPMCs were significantly decreased compared with those of LPS group (0.77±0.08 vs 0.90±0.10, P<O.01; 0.79±0.16 vs 0.99±0.06, P<0.05; 0.83±0.20 vs 1.22±0.13, P<0.05). However, for the group pretreated with rosiglitazone(10 μmol/L) and GW9662(3 μmol/L) for 3 h then added with LPS, the levels of p-p65 in RPMCs did not change significantly compared with those of rosiglitazone-pretreated group. The expressions of CD40 and ICAM-1 in RPMCs were significantly increased compared with those of rosiglitazone-pretreated group (0.95±0.19 vs 0.79±0.16, and 1.04±0.24 vs 0.83±0.20, P<0.05). Conclusion Rosiglitazone can decrease LPS-induced expression of CD40 and ICAM-1 in RPMCs by inhibition of NF-κB activation, which suggests that rosiglitazone may mediate its antiinflammatory effect through a NF-κB dependent mechanism.