Expression of monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 by human airway smooth-muscle cells - Modulation by corticosteroids and T-helper2 cytokines

We have demonstrated that, in addition to their contractile function, human airway smooth-muscle cells (HASMC) are able to express and to secrete chem okines of the monocyte chemotactic protein (MCP)/eotaxin subfamily. This gr oup 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 regulat ed on activation, normal T cells expressed and secreted (RANTES) mRNA in HA SMC in culture. HASMC express MCP and RANTES mRNA after stimulation with in terleukin (IL)-1 beta, tumor necrosis factor-alpha, and interferon-gamma. M CP mRNA was maximal at 8 h, whereas RANTES mRNA expression was delayed to 2 4 h after stimulation. Further, significant differences were observed in th e induction patterns of MCP and RANTES mRNA expression after stimulation wi th the individual cytokines. Dexamethasone (DEX) significantly inhibited cy tokine-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 chemokin e expression. The cytokine-induced MCP mRNA expression in HASMC was associa ted with MCP release, which was inhibited by DEX and post-translationally b y 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 characte ristic of allergic airway diseases.