IL-4 and IFN-gamma increase steady state levels of polymeric Ig receptor mRNA in human airway and intestinal epithelial cells

Delivery of IgA. to the mucosal surface occurs via transcytosis of polymeri c Igh (pIgA) across the epithelium, a process mediated by the pIgR. Several factors increase pIgR expression in human epithelial cells, including IL-4 and IFN-gamma, Using an RNase protection assay, we found that IL-4 and IFN -gamma increase steady state levels of pIgR mRNA in both human intestinal ( HT29) and airway (Calu-3) epithelial cells. Time course studies in HT29 clo ne 19A cells showed that with each cytokine alone and with both together: 1 ) there was a significant lag before mRNA levels increased; 2) maximal leve ls were not reached until 48-72 h after the addition of cytokines; 3) mRNA levels remained elevated in the continued presence of cytokines: and 4) add ition of actinomycin D or removal of cytokines led to decreases in mRNA lev els with a half-life of similar to 20-28 h. Cytokine-dependent increases in steady state levels of pIgR mRNA were inhibited by cycloheximide and by pr otein tyrosine kinase inhibitors but not by inhibitors of protein kinase C or cAMP-dependent protein kinase A, Both IFN-gamma and IL-I increased expre ssion of the inducible transcription factor IFN regulatory factor-1 (IRF-1) , but levels of IRF-1 only weakly correlated with levels of pIgR mRNA, sugg esting that additional transcription factors are required. These studies pr ovide additional insights into the mechanisms by which cytokines regulate e xpression of the pIgR, a central player in mucosal immunity.