MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis

MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta 1 Plus cytomix (a mixture of IL-1 beta, IFN-gamma and TNF-alpha). TGF-beta 1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 +/- 0.6% of control vs 83.1 +/- 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 +/- 1.5%, p < 0.01). In contrast, a miRNA-146a, inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling. (C) 2009 Elsevier Inc. All rights reserved