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Am J Physiol Lung Cell Mol Physiol 280: L675-L679, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 4, L675-L679, April 2001

IL-1beta enhances beta 2-adrenergic receptor expression in human airway epithelial cells by activating PKC

Wei Bin, Mark O. Aksoy, Yi Yang, and Steven G. Kelsen

Pulmonary Division, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Protein kinase C (PKC)-activated signal transduction pathways regulate cell growth and differentiation in many cell types. We have observed that interleukin (IL)-1beta upregulates beta 2-adrenergic receptor (beta 2-AR) density and beta 2-AR mRNA in human airway epithelial cells (e.g., BEAS-2B). We therefore tested the hypothesis that PKC-activated pathways mediate IL-1beta -induced beta -AR upregulation. The role of PKC was assessed from the effects of 1) the PKC activator phorbol 12-myristate 13-acetate (PMA) on beta -AR density, 2) selective PKC inhibitors (calphostin C and Ro-31-8220) on beta -AR density, and 3) IL-1beta treatment on the cellular distribution of PKC isozymes. Recombinant human IL-1beta (0.2 nM for 18 h) increased beta -AR density to 213% of control values (P < 0.001). PMA (1 µM for 18 h) increased beta -AR density to 225% of control values (P < 0.005), whereas Ro-31-8220 and calphostin C inhibited the IL-1beta -induced upregulation of beta -AR in dose-dependent fashion. PKC isozymes detected by Western blotting included alpha , beta II, epsilon , µ, zeta , and lambda /iota . IL-1beta increased PKC-µ immunoreactivity in the membrane fraction and had no effect on the distribution of the other PKC isozymes identified. These data indicate that IL-1beta -induced beta -AR upregulation is mimicked by PKC activators and blocked by PKC inhibitors and appears to involve selective activation of the PKC-µ isozyme. We conclude that signal transduction pathways activated by PKC-µ upregulate beta 2-AR expression in human airway epithelial cells.

cytokines; gene expression; airway inflammation; signal transduction; interleukin-1beta ; protein kinase C


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