TNFR/TNF-α signaling pathway regulates apoptosis of alveolar macrophages in coal workers' pneumoconiosis.

Autor:	Qian QZ; School of Public Health, North China University of Science and Technology, Tangshan 063000, P.R. China., Cao XK; College of Life Sciences, North China University of Science and Technology, Tangshan 063000, P.R. China., Liu HY; School of Public Health, North China University of Science and Technology, Tangshan 063000, P.R. China., Zheng GY; School of Public Health, North China University of Science and Technology, Tangshan 063000, P.R. China., Qian QQ; Department of Neurology, Tangshan Gongren Hospital Affiliated to North China University of Science and Technology, Tangshan 063000, P.R. China., Shen FH; School of Public Health, North China University of Science and Technology, Tangshan 063000, P.R. China.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Jul 01; Vol. 9 (1), pp. 1302-1310. Date of Electronic Publication: 2017 Jul 01 (Print Publication: 2018).
DOI:	10.18632/oncotarget.18921
Abstrakt:	We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression). We found thatAM apoptosis washigher amongCWP patients than thehealthycontrols. Expression ofBcl-2, Caspase-3 and Caspase-8 was higher inAMs from CWP patientsthan in those from the controlsand correlated with increased AM apoptosis. Univariate and multivariate analyses suggested that CWP grade, initial exposure time, exposure time inyears, and CWP onset agewereall associated with altered levels of Bcl-2, Caspase-3 and Caspase-8. Inhibition of TNFR/TNF-α signaling usinganti-TNFR antibody, SOD or NFkB inhibitionreduced AM apoptosisand decreased Bcl-2, Caspase-3 and Caspase-8 expression. These data suggestinhibition of a TNFR/TNF-α signaling pathway is a potentiallyeffective means ofalleviating CWP by inhibiting AM apoptosis. Competing Interests: CONFLICTS OF INTEREST All authors in our study have no conflicts of interest.
Databáze:	MEDLINE
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