Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium

Zhi Hua Chen, Yin Fang Wu, Ping Li Wang, Yan Ping Wu, Zhou Yang Li, Yun Zhao, Jie Sen Zhou, Chen Zhu, Chao Cao, Yuan Yuan Mao, Feng Xu, Bei Bei Wang, Stephania Cormier, Song Min Ying, Wen Li, Hua Hao Shen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.

Original languageEnglish (US)
Pages (from-to)297-311
Number of pages15
JournalAutophagy
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2016

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Particulate Matter
Autophagy
Mucus
Epithelium
Inflammation
Epithelial Cells
Interleukin-8
Transcription Factor AP-1
Wounds and Injuries
Endocytosis
Ultrafine
Free Radicals
Interleukin-6
Cytokines
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Chen, Z. H., Wu, Y. F., Wang, P. L., Wu, Y. P., Li, Z. Y., Zhao, Y., ... Shen, H. H. (2016). Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. Autophagy, 12(2), 297-311. https://doi.org/10.1080/15548627.2015.1124224

Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. / Chen, Zhi Hua; Wu, Yin Fang; Wang, Ping Li; Wu, Yan Ping; Li, Zhou Yang; Zhao, Yun; Zhou, Jie Sen; Zhu, Chen; Cao, Chao; Mao, Yuan Yuan; Xu, Feng; Wang, Bei Bei; Cormier, Stephania; Ying, Song Min; Li, Wen; Shen, Hua Hao.

In: Autophagy, Vol. 12, No. 2, 01.01.2016, p. 297-311.

Research output: Contribution to journalArticle

Chen, ZH, Wu, YF, Wang, PL, Wu, YP, Li, ZY, Zhao, Y, Zhou, JS, Zhu, C, Cao, C, Mao, YY, Xu, F, Wang, BB, Cormier, S, Ying, SM, Li, W & Shen, HH 2016, 'Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium', Autophagy, vol. 12, no. 2, pp. 297-311. https://doi.org/10.1080/15548627.2015.1124224
Chen, Zhi Hua ; Wu, Yin Fang ; Wang, Ping Li ; Wu, Yan Ping ; Li, Zhou Yang ; Zhao, Yun ; Zhou, Jie Sen ; Zhu, Chen ; Cao, Chao ; Mao, Yuan Yuan ; Xu, Feng ; Wang, Bei Bei ; Cormier, Stephania ; Ying, Song Min ; Li, Wen ; Shen, Hua Hao. / Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. In: Autophagy. 2016 ; Vol. 12, No. 2. pp. 297-311.
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