Role of cAMP signaling in mucin production in response to IL‐13 in human bronchial epithelial cells (660.12)

Abstract

Asthma, a chronic airway inflammatory disease, is associated with mucus hypersecretion by airway epithelium. Accumulated mucus leads to airway obstruction and morbidity. We have shown that β2AR signaling has pro‐inflammatory effects in cultured normal human bronchial epithelial cells (NHBECs) in response to IL‐13(1). Our objective here was to elucidate the role of cAMP signaling in mucin production.NHBECs growing at air‐liquid interface (ALI) were subjected to various treatments, and levels of MUC5AC transcripts, intracellular mucin, cAMP levels, pCREB and pSTAT6 were measured on day 14 ALI.Treatment with forskolin+IBMX (to raise global intracellular cAMP levels) increased MUC5AC transcripts and intracellular mucin in the presence or absence of epinephrine in response to IL‐13 pCREB and pSTA6 were also elevated only in the presence of epinephrine, IL‐13 and forskolin+IBMX. A compartmentalized increase in cAMP caused by treatment with roflumilast, a PDE4 inhibitor, did not affect MUC5AC expression but reduced intracellular mucin only in the presence of epinephrine+IL‐13. Roflumilast did not affect the levels of cAMP, pCREB or pSTAT6.Our data provide evidence for the different influences of global and compartmentalized increases in cAMP on mucin production in human airway epithelium in response to IL‐13.1.Pokkunuri et al, BPS, 2011 Winter MeetingGrant Funding Source: Supported by NIH 1RO1A179236 awarded to RAB and BJK