Tanshinone IIA-regulation of IL-6 antagonizes PM 2 .5 -induced proliferation of human bronchial epithelial cells via a STAT3/miR-21 reciprocal loop.

Particulate matter 2.5 (PM 2.5 ), a component of atmospheric particulate matter, leads to changes in gene expression and cellular functions. Epidemiological evidence confirms that PM 2.5 has a positive correlation with lung injury. However, the molecular mechanisms involved remain poorly understood, and preventive methods are needed. In the present study, with human bronchial epithelial (HBE) cells in culture, we showed that low concentrations of PM 2.5 resulted in acceleration of the G1/S transition and cell proliferation. Consistent with these effects, expression of the pro-inflammatory factor interleukin-6 (IL-6) was elevated in HBE cells exposed to PM 2.5 . Accordingly, signal transducer and activator of transcription 3 (STAT3) was activated, which down-regulated expression of cyclin D1. In addition, PM 2.5 exposure led to higher levels of miR-21, and there was a reciprocal loop between miR-21 and STAT3. For HBE cells, tanshinone IIA (Tan IIA) reversed the PM 2.5 -induced cell cycle alteration and cell proliferation, and reduced the expression of cytokines (IL-6, STAT3, and miR-21). These results show that, for HBE cells, Tan IIA attenuates the PM 2.5 -induced G1/S alteration and cell proliferation, and indicate that it has potential clinical application for PM 2.5 -induced respiratory injuries.