IL-1beta enhances beta2-adrenergic receptor expression in human airway epithelial cells by activating PKC.
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 beta2-adrenergic receptor (beta2-AR) density and beta2-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 microM 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, betaII, epsilon, mu, zeta, and lambda/iota. IL-1beta increased PKC-mu 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-mu isozyme. We conclude that signal transduction pathways activated by PKC-mu upregulate beta2-AR expression in human airway epithelial cells.
Pulmonary Division, Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
W
W
Bin
M O
MO
Aksoy
Y
Y
Yang
S G
SG
Kelsen
D002461:Cell Line, Transformed; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011994:Recombinant Proteins; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism*
D007375:Interleukin-1; D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D011493:Protein Kinase C