Release of granulocyte-macrophage colony stimulating factor by human cultured airway smooth muscle cells: suppression by dexamethasone

Abstract

Smooth muscle cells represent a significant percentage of the total cells in the airway but their contribution to the inflammatory response seen in airway disease has not been studied. Hence, we have looked at the release of the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in response to bacterial lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1β (IL-1β), tumour necrosis factor α (TNFα) and interferon γ (IFNγ). Human airway smooth muscle (HASM) cells released GM-CSF under basal conditions (45.4±13.1 pg ml⁻¹) that was significantly enhanced by IL-1β and TNFα with a maximal effect seen at 10 ng ml⁻¹ (1.31±0.07 ng ml⁻¹ and 0.72±0.16 ng ml⁻¹, respectively). In contrast, neither LPS nor IFNγ produced a significant increase in GM-CSF release. However, HASM cells exposed to IL-1β, TNFα and IFNγ generated more GM-CSF than that evoked by any cytokine alone (2.2±0.15 ng ml⁻¹). The release of GM-CSF elicited by the cytokine mixture was inhibited by cycloheximide and dexamethasone. These data suggest that HASM cells might play an active part in initiating and/or perpetuating airway inflammation in addition to controlling airway calibre.

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