Secreted Factors from Human Mast Cells Trigger Inflammatory Cytokine Production by Human Airway Smooth Muscle Cells

Background: A notable feature of allergic asthma is the infiltration of mast cells into smooth muscle in the human airway. Thus, mast cells and human airway smooth muscle (hASM) cells are likely to exhibit mutual functional modulation via direct cell-cell contact or through released factors. This study examined mast cell modulation of hASM cell cytokine release. Methods: The mast cell line HMC alpha was used to model mast cell function. hASM cells were either co-cultured directly with resting or IgE/antigen-stimulated HMC alpha cells or treated with HMC alpha-conditioned media to examine the impact on cytokine release. The activation pathways triggered in hASM cells by the mast cell-derived factors were examined through the use of selective inhibitors and by Western blotting. Results: HMC alpha cells, or their conditioned media, induced the expression of cytokines (IL-8 and IL-6) by hASM cells at both the mRNA and the protein level. Cytokine expression in hASM cells was greatly amplified when HMC alpha cells were IgE/antigen-activated. The effects of the conditioned media were not mediated by the chemokines MCP-1 and MIP-1 alpha or by exosomes. While the mast cell-derived factor(s) increased p38(MAPK) phosphorylation in hASM cells, cytokine production was not inhibited by the p38(MAPK) inhibitor SB203580. hASM cell production of IL-8 induced by HMC alpha condition media but not IL-6 was, however, attenuated by the Src tyrosine kinase inhibitor PP2. Conclusions: Our study shows that the release of soluble mediators by activated mast cells can stimulate hASM cells to elicit production of proinflammatory cytokines that may then exacerbate airway inflammation in asthma. Copyright (c) 2012 S. Karger AG, Basel