ERK/Egr-1 signaling pathway is involved in CysLT2 receptor-mediated IL-8 production in HEK293 cells |
| |
Authors: | Kana Lin Sanhua Fang Beilei Cai Xueqin Huang Xiayan Zhang Yunbi Lu Weiping Zhang Erqing Wei |
| |
Institution: | 1. Department of Pharmacology and Institute of Neuroscience, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China;2. Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), School of Medicine, Zhejiang University, 1511 Jianghong Road, Hangzhou 310052, PR China |
| |
Abstract: | The CysLT2 receptor is involved in myocardial ischemia/reperfusion injury, differentiation of colorectal cancers, bleomycin-induced pulmonary inflammation and fibrosis. However, the signal transduction of cysteinyl leukotriene receptor 2 (CysLT2) in inflammatory responses remains to be clarified. In HEK293 cells stably expressing hCysLT1, hCysLT2 and rGPR17, we determined the signaling pathways for interleukin-8 (IL-8) production after CysLT2 receptor activation. HEK293 cells were stably transfected with the recombinant plasmids of pcDNA3.1(+)-hCysLT1, pcDNA3.1(+)-hCysLT2 and pcDNA3.1-rGPR17. Leukotriene C4 (LTC4) and LTD4 were used as the agonists to induce IL-8 production and the related changes in signal molecules. We found that LTC4 and LTD4 significantly induced IL-8 promoter activation in the HEK293 cells stably expressing hCysLT2, but not in those expressing hCysLT1 and rGPR17. In hCysLT2-HEK293 cells, LTC4 induced elevation of intracellular calcium, ERK1/2 phosphorylation and Egr-1 expression, and stimulated IL-8 expression and release. These responses were blocked by the selective CysLT2 receptor antagonist HAMI3379. The ERK1/2 inhibitor U0126 inhibited Egr-1 and IL-8 expression as well as IL-8 release, but the JNK and p38 inhibitors did not have the inhibitory effects. Down-regulation of Egr-1 by RNA interference with its siRNA inhibited the LTC4-induced IL-8 expression and release. In conclusion, these findings indicate the ERK-Egr-1 pathway of CysLT2 receptors mediates IL-8 production induced by the pro-inflammatory mediators LTC4 and LTD4. |
| |
Keywords: | Cysteinyl leukotriene receptor 2 Signal transduction Interleukin-8 Extracellular signal-regulated kinase Early growth response-1 |
本文献已被 ScienceDirect 等数据库收录! |
|