Tanshinone IIA-regulation of IL-6 antagonizes PM2.5-induced proliferation of human bronchial epithelial cells via a STAT3/miR-21 reciprocal loop

Particulate matter 2.5 (PM2.5), a component of atmospheric particulate matter, leads to changes in gene expression and cellular functions. Epidemiological evidence confirms that PM2.5 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 PM2.5 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 PM2.5. Accordingly, signal transducer and activator of transcription 3 (STAT3) was activated, which down-regulated expression of cyclin D1. In addition, PM2.5 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 PM2.5-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 PM2.5-induced G1/S alteration and cell proliferation, and indicate that it has potential clinical application for PM2.5-induced respiratory injuries.

Automated summary

PM2.5 exposure induces changes in gene expression and cellular functions in human bronchial epithelial cells, and is positively correlated with lung injury. Tanshinone IIA can reverse the cell cycle alteration and cell proliferation caused by PM2.5.