different signal pathways regulate il-1β-induced mature and primary mirna-146a expression in human alveolar epithelial cells

it was known that il-1β-induced rapid expression of mir-146a, which regulated the secretion of inflammatory chemokines in human a549 alveolar epithelial cells. however, little is known about the level of primary mir-146a and the downstream biogenesis of mir-146a in a549 cells. we examined the levels of primary mir-146a and mature mir-146a in a549 cells following treatment with pharmacological inhibitors of ikk-2 (tpca-1), mek-1/2 (pd098059), jnk-1/2 (sp600125), p38 mapk (sb 203580) and pi-3k (ly294002). our studies showed that exposure to pd98059, tpca-1 and ly294002 resulted in a dose-dependent reduction in the expression of mature mir-146a while the primary mir-146a expression was not changed by any inhibitor. western blot showed that il-1β induced an increase of trbp at 30 min, following by an extended expression at 24 h compared to the non-il-1β controls in a549 cells. in conclusion, our studies indicated that mir-146a expression in alveolar epithelial cells was regulated at the post-transcriptional level via a mek-1/2 and ikk2 pathway, and also for the first time via pi-3k pathway. the longer expression of trbp following stimulation with il-1β suggests that trbp might play a role in the process of regulating the processing of primary mir-146a to mature mir-146a in human alveolar epithelial cells.