Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Republic of Korea.
Arch Pharm Res. 2017 Jul;40(7):854-863. doi: 10.1007/s12272-017-0927-9. Epub 2017 Jun 22.
Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (HO)-induced HepG2 cells by using FSLLRY-NH a PAR2 antagonist. HO treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells. Treatment with HO at concentrations above 400 μM for 24 h also reduced HepG2 cell viability. HO treatment increased both the protein and mRNA levels of IL-1β, IL-8, and TNF-α, as well as those of SAPK/JNK. The increased levels of these pro-inflammatory genes and SAPK/JNK induced by HO were attenuated in a dose-dependent manner when cells were co-treated with HO and FSLLRY-NH2. In summary, the PAR2 antagonist peptide, FSLLRY-NH2, reduces the level of the pro-inflammatory genes IL-8, IL-1β, and TNF-α induced by HO, through the SAPK/JNK pathways in HepG2 cells. These data suggest that a PAR2 antagonist could be an anti-inflammatory agent in HepG2 cells.
蛋白酶激活受体 2（PAR2）位于胃肠道、呼吸系统和肾小管中，是一种与炎症、代谢和疾病相关的 G 蛋白偶联受体。本研究旨在通过使用 PAR2 拮抗剂 FSLLRY-NH2 来探讨 PAR2 在过氧化氢（HO）诱导的 HepG2 细胞中的作用。HO 处理导致食管、胃和肝细胞中 PAR2 的诱导，其中 HepG2 细胞的反应最强烈。此外，这种效应在 HepG2 细胞中呈剂量依赖性。用浓度高于 400 μM 的 HO 处理 24 小时也降低了 HepG2 细胞的活力。HO 处理增加了 IL-1β、IL-8 和 TNF-α以及 SAPK/JNK 的蛋白和 mRNA 水平。当细胞用 HO 和 FSLLRY-NH2 共同处理时，HO 诱导的这些促炎基因和 SAPK/JNK 的增加水平呈剂量依赖性降低。总之，PAR2 拮抗剂肽 FSLLRY-NH2 通过 SAPK/JNK 途径降低了 HO 诱导的 HepG2 细胞中促炎基因 IL-8、IL-1β 和 TNF-α的水平。这些数据表明，PAR2 拮抗剂可能是 HepG2 细胞中的一种抗炎剂。
