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

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 re...