Calcitonin gene-related peptide inhibits interleukin-1 beta-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-beta (IL-1 beta) 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 beta-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 hCGRP(8-37) (0.1-1 nmol-L-1) greatly amplified IL-1 beta-induced IL-8 production. The inhibition of CGRP expression by siRNA significantly increased IL-8 secretion upon IL-1 beta stimulation. However, cell clones stably transfected with CGRP showed significantly inhibited mRNAandproteinlevelsofIL-8 inducedbyIL-1 beta. Conclusion: These data imply that AEII cell-derived CGRP suppress IL-1 beta-induced IL-8 secretion in an autocrine/paracrine mode. Further investigation showed that CGRP attenuated IL-1 beta-aroused ROS formation, which is an early indication of pro-inflammatory factor signaling.Chemistry, MultidisciplinaryPharmacology & PharmacySCI(E)PubMed中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)5ARTICLE101340-13452