Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells
Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells
复制标题
DOI：
10.4049/jimmunol.168.7.3577
复制
发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Stewart, GA
中科院分区：
文献类型：
--
作者：
Asokananthan, N;Graham, PT;Stewart, GA
许多组织的上皮细胞表达蛋白酶激活受体 (PAR)，在多种不同的生理过程中发挥重要作用。在这项研究中，我们检查了它们在 A459 和 BEAS-2B 细胞系以及原代人支气管上皮细胞 (HBEC) 中调节 IL-6、IL-8 和 PGE(2) 产生的能力。通过 RT-PCR 和免疫细胞化学判断，所有三种细胞类型均表达 PAR-1、PAR-2、PAR-3 和 PAR-4。对应于 PAR-1、PAR-2 和 PAR-4 新生 N 末端的激动剂肽诱导 A549、BEAS-2B 和 HBEC 释放细胞因子，在 400 mum 时，效力顺序为 PAR-2 > PAR-4 > PAR-1。 PAR-1、PAR-2 和 PAR-4 还导致 A549 和 HBEC 释放 PGE(2)。 PAR-3 激动剂肽在所有测试系统中均无活性。 PAR-1、PAR-2或PAR-4组合引起IL-6累加释放，但只有PAR-1和PAR-2组合导致累加IL-8反应。 PAR 肽诱导的反应伴随着细胞内钙离子浓度的变化。然而，PAR-4 的 Ca2+ 离子关闭速度比 PAR-1 或 PAR-2 慢 2 倍，表明 G 蛋白偶联存在差异。综合起来，这些数据表明 PAR 在调节肺部炎症中发挥着重要作用。
Epithelia from many tissues express protease-activated receptors (PARs) that play a major role in several different physiological processes. In this study, we examined their capacity to modulate IL-6, IL-8, and PGE(2) production in both the A459 and BEAS-2B cell lines and primary human bronchial epithelial cells (HBECs). All three cell types expressed PAR-1, PAR-2, PAR-3, and PAR-4, as judged by RT-PCR and immunocytochemistry. Agonist peptides corresponding to the nascent N termini of PAR-1, PAR-2, and PAR-4 induced the release of cytokines from A549, BEAS-2B, and HBECs with a rank order of potency of PAR-2 > PAR-4 > PAR-1 at 400 mum. PAR-1, PAR-2, and PAR-4 also caused the release of PGE(2) from A549 and HBECs. The PAR-3 agonist peptide was inactive in all systems tested. PAR-1, PAR-2, or PAR-4, in combination, caused additive IL-6 release, but only the PAR-I and PAR-2 combination resulted in an additive IL-8 response. PAR peptide-induced responses were accompanied by changes in intracellular calcium ion concentrations. However, Ca2+ ion shutoff was similar to2-fold slower with PAR-4 than with PAR-1 or PAR-2, suggesting differential G protein coupling. Combined, these data suggest an important role for PAR in the modulation of inflammation in the lung.