Mesenchymal Stem Cells Reduce Cigarette Smoke-Induced Inflammation and Airflow Obstruction in Rats via TGF-β1 Signaling

Abstract

Cigarette smoke has been shown to cause chronic inflammation of the lungs, eventually leading to chronic obstructive pulmonary disease (COPD). Additionally, recent studies have suggested that mesenchymal stem cells (MSCs) can mediate local inflammatory responses in the lungs. Thus, the aim of the present study was to test the effects of rat MSCs (rMSCs) on inflammation of the lungs and destructive pulmonary function induced by cigarette smoke in rats. Rats were exposed to cigarette smoke for 7 weeks. rMSCs were cultured in vitro and infused intratracheally into cigarette smoke-exposed rats. The total and differential cell counts in the bronchoalveolar lavage fluid (BALF), histological changes, pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) expression, and pulmonary function were evaluated. Additionally, human peripheral blood mononuclear cells and human MSCs were cocultured in vitro to detect cytokines and TGF-β1 levels. We found that rMSC administration resulted in downregulation of pro-inflammatory cytokines in the lungs while increasing TGF-β1 expression, reducing total inflammatory cell numbers in the BALF, and improving pulmonary histopathology and airflow obstruction. Coculture revealed that human MSCs mediated an anti-inflammatory effect partly via upregulation of TGF-β1. These findings suggested that MSCs may have therapeutic potential in cigarette smoke-induced inflammation and airflow obstruction, partly via upregulation of TGF-β1.

Keywords :

• inflammation
• mesenchymal stem cell
• transforming growth factor-β1

Acknowledgments

Authors Song and Guan contributed equally to this work. We would like to thank the staff of the Molecular and Biology Laboratory of Xinhua Hospital for their assistance.

Declaration of Interest Statement

The authors indicate that there are no potential conflicts of interest to declare. The authors are responsible for the content and writing of this paper.

This work was supported by grants from the Support Program of Shanghai Science and Technology Committee (No. 12431900701), Youth Project of Shanghai Municipal Public Health Bureau (No. 2009Y024) and State Natural Sciences Foundation Project (No. 81000014).