Proliferation of Lung Epithelial Cells Is Regulated by the Mechanisms of Autophagy Upon Exposure of Soots

Rituraj Niranjan; Kaushal Prasad Mishra; Sachchida Nand Tripathi; Ashwani Kumar Thakur

doi:10.3389/fcell.2021.662597

Proliferation of Lung Epithelial Cells Is Regulated by the Mechanisms of Autophagy Upon Exposure of Soots

Front Cell Dev Biol. 2021 Jul 21:9:662597. doi: 10.3389/fcell.2021.662597. eCollection 2021.

Authors

Rituraj Niranjan^{1

2}, Kaushal Prasad Mishra¹, Sachchida Nand Tripathi³, Ashwani Kumar Thakur¹

Affiliations

¹ Laboratory 6, Department of Biological Sciences and Bioengineering (BSBE), Indian Institute of Technology, Kanpur, India.
² Talent Search Scientist (TSS-ICMR), currently at, Immunology Laboratory, ICMR-Vector Control Research Centre, Puducherry, India.
³ Department of Civil Engineering, Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur, India.

Abstract

Background: Soots are known to cause many diseases in humans, but their underlying mechanisms of toxicity are still not known. Here, we report that soots induce cell proliferation of lung epithelial cells via modulating autophagy pathways.

Results: Fullerene soot and diesel exhaust particles (DEP) induced cell proliferation of lung epithelial, A549 cells via distinct autophagic mechanisms and did not cause cell death. Exposure of fullerene soot protected the cell death of A549 cells, caused by hydrogen peroxide, and inhibited LPS-induced autophagy. Fullerene soot co-localized with the autophagic proteins and inhibited starvation-induced autophagy (downregulated ATG-5, beclin-1, p62, and LC3 expressions) independent of its antioxidant properties. Similarly, it decreased the expression profile of autophagic genes and upregulated the proliferation-responsive gene, Ki-67, in mice. We observed that expressions of fullerene soot-responsive genes (Beclin-1, ATG-5, and p62) were reverted by Akt Inhibitor X, indicating an important role of the Akt pathway. At an elemental level, we found that elemental carbon of fullerene soot may be converted into organic carbon, as measured by OCEC, which may point fullerene soot as a source of carbon. On the other hand, DEP upregulated the expressions of autophagy genes. Akt Inhibitor X did not attenuate DEP-induced cell proliferation and autophagic response. However, an autophagic inhibitor, chloroquine, and significantly inhibited DEP-induced cell proliferation.

Conclusion: It can be said that distinct autophagic mechanisms are operational in cell proliferation of lung epithelial cells due to soots, which may be responsible for different diseases. Understanding the mechanism of these pathways provides some important targets, which can be utilized for the development of future therapeutics.

Keywords: autophagy; cell proliferation; environmental soots; fullerene soot; p62/SQSTM1; particulate matter; pollutants (environmental); reactive oxygen species.