PPAR-γ激动剂抑制IFN-γ和TNF-α诱导的肾小管上皮细胞趋化因子表达

PPAR-γ agonist inhibits the expressions of chemokines induced by IFN-γ and TNF-α in renal tubular epithelial cells

目的探讨过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂15-脱氧-12,14-前列腺素J2(15d-PGJ2)对IFN-γ和TNF-α共同诱导HK-2肾小管上皮细胞趋化因子表达的影响。方法在IFN-γ和TNF-α联合刺激HK-2细胞的同时加入不同浓度的15d-PGJ2共同作用48 h,用实时定量PCR(qRT-PCR)和ELISA分别检测CXCL9、CXCL10和CXCL11的mRNA表达和蛋白分泌水平。结果在HK-2细胞中,IFN-γ和TNF-α联合刺激能够诱导趋化因子CXCL9、CXCL10、CXCL11的mRNA表达和蛋白分泌;经不同浓度的15d-PGJ2干预后,CXCL9、CXCL10、CXCL11的mRNA表达和蛋白分泌均被抑制,在15d-PGJ2浓度为2.0 ng/mL时,15d-PGJ2对CXCL9、CXCL10、CXCL11的mRNA和蛋白分泌的影响最大,与IFN-γ联合TNF-α组(15d-PGJ2浓度为0 ng/mL)相比,CXCL9、CXCL10、CXCL11的mRNA分别下降76.8%、78.7%和81.9%,培养上清中趋化因子蛋白分泌分别下降66.9%、86.6%和39.9%,差异均有统计学意义(P<0.05)。结论 PPAR-γ激动剂可抑制IFN-γ和TNF-α联合作用诱导的肾小管上皮细胞趋化因子CXCL9、CXCL10和CXCL11表达。

Objective To investigate the effect of peroxisome proliferator-activated receptor-γ （PPAR-γ） agonist 15d-PGJ2 on the expressions of CXCL9, CXCL10 and CXCL11 in renal tubular epithelial cells （HK-2） stimulated by interferon-）, （IFN-γ） plus tumor necrosis factor-α （TNF-α）. Methods HK-2 cells were stimulated with IFN-γ plus TNF-α only, or incubated with 15d-PGJ2 for48 hours. CXCL9, CXCL10 and CXCL11 expressions were determined by real-time quantitative PCR （qRT-PCR） and ELISA. Results IFN-γ plus TNF-α increased mRNA and protein expressions of CXCLg, CXCL10 and CXCL11 in HK-2 cells. PPAR-γ agonist 15d-PGJ2 inhibited the expressions of CXCL9, CXCL10 and CXCL11 in IFN-γ combined with TNF-α-induced HK-2 cells. Compared with the IFN-γ plus TNF-α group （untreated with 15d-PGJ2）, the CXCL9, CXCL10 and CXCL11 were depressed by 76.8%, 78.7% and 81.9% at mRNA level and 66.9%, 86.6% and 39.9% at protein level in 2.0 ng/mL 15d-PGJ2-treated HK-2 cells, respectively （ P 〈 0.05）. Conduslon PPAR-γ agonist 15d-PGJ2 could inhibit CXCL9, CXCL10 and CXCL11 production induced by IFN-γ combined with TNF-α in HK-2 cells.