Extracellular signal-regulated kinase1/2 signalling pathway regulate the secretions of human bronchial smooth muscle cells passively sensitized by asthmatic serum
Objectives: To investigate the role of extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathway in the secretion of human bronchial smooth muscle cells passively sensitized by asthmatic serum. Methods: Human bronchial smooth muscle cells (HBSMCs) were taken from normal pulmonary tissue in surgery and cultured in vitro treated with normal human serum or asthmatic serum. Epidermal growth factor, PD98059 and ERK1/2 antisense oligonucleotide were used to explore the role of ERK1/2 signaling pathway. The expression of Phospho-ERK1/2 in HBSMCs was analyzed by Western blot. Secretion of HBSMCs was detected by enzyme linked immunosorbent assay and Western blot. Results: The level of Phospho-ERK1/2 increased in HBSMCs passive sensitized with asthmatic serum compared with normal serum. HB-SMCs of asthmatic serum group secreted much more growth factors (TGF-beta 1, VEGF and CTGF), cytokines (RANTES and EOTAXIN) and extracellular matrix (Fibronectin and CollangenI) than that of normal controls. Epidermal growth factor stimulated the secretions of both two groups, but the response of chronic asthmatic group was more intense. Both PD98059 and antisense oligonucleotide were able to suppress the secretions of passive sensitized HBSMCs, but antisense oligonucleotide reduced the level of RANTES nearly to that of normal controls, while PD98059 couldn't. Conclusion: Our results suggest that ERK1/2 signalling pathway may play an important role in the increased secretion of passive sensitized HBSMCs, and ERK1/2 antisense oligonucleotide is capable to slow down the process.
基金:
National Natural Science Foundation of China [30900648]