Effects of glucocorticoids and Protein Kinase A on growth factor- and 1beta- regulated gene

Glucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma - excessive ASM growth are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as interleukin 1beta and tumor necrosis factor alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and interleukin 1beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis.

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Misior AM, Deshpande DA, Loza MJ, Pascual RM, Hipp JD, Penn RB