Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway

Junyan Yan; Chia-Hsiang Lai; Shih-Chun Candice Lung; Chongjun Chen; Wen-Cheng Wang; Pin-I Huang; Chia-Hua Lin

doi:10.1016/j.scitotenv.2017.05.107

Industrial PM_2.5 cause pulmonary adverse effect through RhoA/ROCK pathway

Sci Total Environ. 2017 Dec 1:599-600:1658-1666. doi: 10.1016/j.scitotenv.2017.05.107. Epub 2017 May 19.

Authors

Junyan Yan¹, Chia-Hsiang Lai², Shih-Chun Candice Lung³, Chongjun Chen⁴, Wen-Cheng Wang³, Pin-I Huang⁵, Chia-Hua Lin⁶

Affiliations

¹ Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; University of Chinese Academy of Sciences, Beijing 100039, China.
² Department of Safety Health and Environmental Engineering, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan.
³ Research Center for Environmental Changes, Academia Sinica, Taipei 11529, Taiwan.
⁴ School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
⁵ Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan.
⁶ Department of Biotechnology, National Formosa University, Yunlin 63208, Taiwan. Electronic address: vicchlin@nfu.edu.tw.

PMID: 28535594
DOI: 10.1016/j.scitotenv.2017.05.107

Abstract

According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM_2.5) is associated with adverse health effects, the major action mechanisms of different compositions of PM_2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM_2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM_2.5, including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM_2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM_2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM_2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM_2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM_2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM_2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM_2.5.

Keywords: Cytotoxicity; Fine particulate matter; Organic extract; RhoA/ROCK pathway; Water-soluble extract.