Calcitonin gene-related peptide inhibits interleukin-1β-induced interleukin-8 secretion in human type Ⅱ alveolar epithelial cells  

作　　者：Wen-jing LI Teng-ke WANG Xian WANG 

机构地区：[1]Department of Physiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science,Ministry of Education, Beijing 100083, China

出　　处：《Acta Pharmacologica Sinica》2006年第10期1340-1345,共6页中国药理学报（英文版）

基　　金：Project supported by the Major National Basic Research Program of China(No 2006CB503802);a National Natural Science Foundation of China(No 30330250)

摘　　要：Aim： Our previous data have shown that type Ⅱ alveolar epithelial （AEⅡ） cells express neuropeptide calcitonin gene-related peptide （CGRP）, and that pro-inflammatory factor interleukin 1-β （IL-1 β） induces CGRP secretion in the A549 human AEⅡ cell line. In the present study, we investigated the effect of endogenous and exogenous CGRP on IL- 1 β-induced chemokine interleukin-8 （IL-8） secretion. Methods： We used enzyme-linked immunosorbent assay （ELISA） and RT-PCR to detect IL-8 protein and mRNA levels, respectively, siRNA and the stably transfected cell line were used to knock down and overexpress the CGRP gene, respectively, and chemiluminescence assay was used to detect reactive oxygen species （ROS） formation. Results： CGRP-1 receptor antagonist hCGRP8_37 （0.1^-1 nmol·L^-1） greatly amplified IL- 1 β-induced IL-8 production. The inhibition of CGRP expression by siRNA significantly increased IL-8 secretion upon IL- 1β stimulation. However, cell clones stably transfected with CGRP showed significantly inhibited mRNA and protein levels of IL-8 induced by IL- 1β. Conclusion： These data imply that AEII cell-derived CGRP suppress IL- 1 β-induced IL-8 secretion in an autocrine/ paracrine mode. Further investigation showed that CGRP attenuated IL- 1 β-aroused ROS formation, which is an early indication of pro-inflammatory factor signaling.Aim： Our previous data have shown that type Ⅱ alveolar epithelial （AEⅡ） cells express neuropeptide calcitonin gene-related peptide （CGRP）, and that pro-inflammatory factor interleukin 1-β （IL-1 β） induces CGRP secretion in the A549 human AEⅡ cell line. In the present study, we investigated the effect of endogenous and exogenous CGRP on IL- 1 β-induced chemokine interleukin-8 （IL-8） secretion. Methods： We used enzyme-linked immunosorbent assay （ELISA） and RT-PCR to detect IL-8 protein and mRNA levels, respectively, siRNA and the stably transfected cell line were used to knock down and overexpress the CGRP gene, respectively, and chemiluminescence assay was used to detect reactive oxygen species （ROS） formation. Results： CGRP-1 receptor antagonist hCGRP8_37 （0.1^-1 nmol·L^-1） greatly amplified IL- 1 β-induced IL-8 production. The inhibition of CGRP expression by siRNA significantly increased IL-8 secretion upon IL- 1β stimulation. However, cell clones stably transfected with CGRP showed significantly inhibited mRNA and protein levels of IL-8 induced by IL- 1β. Conclusion： These data imply that AEII cell-derived CGRP suppress IL- 1 β-induced IL-8 secretion in an autocrine/ paracrine mode. Further investigation showed that CGRP attenuated IL- 1 β-aroused ROS formation, which is an early indication of pro-inflammatory factor signaling.

关 键 词：type Ⅱ alveolar epithelial cells INTERLEUKIN-1 INTERLEUKIN-8 calcitonin gene-relatedpeptide ANTI-INFLAMMATION lung reactiveoxygen species 

分 类 号：R78[医药卫生—口腔医学]