Effect of IL-1 beta on responses of cultured human airway smooth muscle cells to bronchodilator agonists.

American Journal of Respiratory Cell and Molecular Biology
S A ShoreR A Panettieri

Abstract

Decreased beta-adrenergic responsiveness is a characteristic feature of asthma. In order to determine whether cytokines released in the asthmatic airway contribute to this phenomenon, we measured changes in stiffness of cultured human airway smooth muscle (HASM) cells induced by isoproterenol (ISO) in control HASM cells and HASM cells pretreated with IL-1 beta (20 ng/ml for approximately 42 h). Stiffness was measured by magnetic twisting cytometry. HASM cells were obtained from normal tracheal tissue obtained at lung transplant, and studied in passages 4-7. In control cells, ISO caused a dose-related decrease in cell stiffness. IL-1 beta had no effect on baseline cell stiffness. However, IL-1 beta caused a rightward shift in the concentration-response curve to ISO and decreased the maximal effectiveness of this agonist. Decreased responses to ISO were also obtained with 2 ng/ml IL-1 beta, or when cells were pretreated with IL-1 beta (20 ng/ml) for 22 h. This effect of IL-1 beta was not altered by pretreatment of the cells with pertussis toxin (100 ng/ml throughout the IL-1 beta exposure period). IL-1 beta also significantly attenuated the ability of prostaglandin E2 (PGE2) to decrease cell stiffness. In contrast, IL-1 beta had ...Continue Reading

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