American Journal of Respiratory Cell and Molecular Biology vol:21 issue:4 pages:528-36
We have demonstrated that, in addition to their contractile function, human airway smooth-muscle cells (HASMC) are able to express and to secrete chemokines of the monocyte chemotactic protein (MCP)/ eotaxin subfamily. This group of chemokines is believed to play a fundamental role in the development of allergic airway diseases such as asthma. The expression levels of MCP (MCP-1, -2, and -3) messenger RNA (mRNA) were compared with those of regulated on activation, normal T cells expressed and secreted (RANTES) mRNA in HASMC in culture. HASMC express MCP and RANTES mRNA after stimulation with interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma. MCP mRNA was maximal at 8 h, whereas RANTES mRNA expression was delayed to 24 h after stimulation. Further, significant differences were observed in the induction patterns of MCP and RANTES mRNA expression after stimulation with the individual cytokines. Dexamethasone (DEX) significantly inhibited cytokine-induced accumulation of MCP and RANTES mRNA, in contrast to IL-4, IL-10, and IL-13, which had no inhibitory effect on cytokine-induced chemokine expression. The cytokine-induced MCP mRNA expression in HASMC was associated with MCP release, which was inhibited by DEX and post-translationally by IL-4. HASMC can actively participate in the pathogenesis of asthma by the expression and release of chemokines, which are likely to play a critical role in the generation and regulation of the inflammatory response characteristic of allergic airway diseases.