Calcitonin gene-related peptide inhibits interleukin-1 -induced interleukin-8 secretion in human type II alveolar epithelial cells
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 interleukin1- (IL-1) 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-induced chemokine interleukin-8 (IL-8) secretion. Methods: We used enzyme-linked immunosorbent assay (ELISA) and RT-PCRto detect IL-8 protein and mRNA levels, respectively. siRNA and the stably trans-fected 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 -induced IL-8 production. The inhibition of CGRP expression by siRNA significantly increased IL-8 secretion upon IL-1 stimulation. However, cell clones stably transfected with CGRP showed significantly inhibited mRNAandproteinlevelsofIL-8 inducedbyIL-1. Conclusion: These data imply that AEII cell-derived CGRP suppress IL-1 -induced IL-8 secretion in an autocrine/paracrine mode. Further investigation showed that CGRP attenuated IL-1 -aroused ROS formation, which is an early indication of pro-inflammatory factor signaling.
Document Type: Research Article
Affiliations: Department of Physiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100083, China
Publication date: 2006-10-01