TNF-α-TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis
Authors: Bin Wang
Xiangke Cao
Yi Qu
Fumin Feng
Zhiqian Sun
Qingzeng Qian
Qingqiang Qian
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: TNF-α-TNFR; alveolar macrophage; apoptosis; autophagy; signal pathway.
Affiliations: College of Public Health, North China University of Science and Technology, Tangshan, China., Hebei Coal Mine Sanitation and Safety Laboratory, Tangshan, China., College of Life Sciences, North China University of Science and Technology, Tangshan, China., Department of Pediatrics, Affiliated Hospital of North China University of Science and Technology, Tangshan, China., Hebei Medical Information Research Institute, Shijiazhuang, China., Department of Internal Medicine-Neurology, Tangshan Worker's Hospital Affiliated to North China University of Science and Technology, Tangshan, China., Occupational Health Technical Service Center, Beidaihe Occupational Disease Prevention and Treatment Hospital of The State Administration of Work Safety, Qinghuangdao, China.

Abstract:  Objective: Exposure to coal dust causes the development of coal worker's pneumoconiosis (CWP), which is associated with accumulating macrophages in the lower respiratory tract. This study was performed to investigate the effect of tumor necrosis factor-α (TNF-α)-tumor necrosis factor receptor (TNFR) signal pathway on autophagy and apoptosis of alveolar macrophages (AMs) in CWP. Methods: AMs from controls exposed to coal dust and CWP patients were collected, in which expressions of TNF-α and TNFR1 were determined. Autophagy was observed by transmission electron microscopy, and apoptosis by light microscope and using terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. AMs in CWP patients were treated with TNF-α or anti-TNF-α antibody. Besides, expressions of autophagy marker proteins, apoptosis-related factors, FAS, caspase-8, and receptor-interacting serine-threonine-protein kinase 3 (RIPK3) were determined by western Blot. Activities of caspase-3 and caspase-8 were determined by a fluorescence kit. Flow cytometry was applied to measure the expression of TNFR1 on the surface of the AM. Results: TNF-α expression and TNFR1 expression on the surface of AM, as well as autophagy and apoptotic index were significantly increased in AMs of CWP patients. In response to the treatment of TNF-α, TNF-α expression and TNFR1 expression on the surface of AM as well as LC3I expression were increased, autophagy was decreased, and LC3, LC3II, Beclin1 and B-cell lymphoma 2 expressions decreased, whereas FAS expression and activity and expression of caspase-3 and caspase-8 increased, and apoptotic index increased. Moreover, the situations were reversed with the treatment of anti-TNF-α antibody. Conclusion: TNF-α-TNFR signal pathway was involved in the occurrence and development of CWP by activating FAS-caspase-8 and thus inhibiting autophagy while promoting apoptosis of AM. 

Retracted: Yes

PubPeer comments:
 Figure 6B. * Red boxes: The PCD40 HEMA5 panels look unexpectedly similar to the PCD70 panels. ![file] , 
 #1 Dear Ms. Bik, thanks for pointing out our mistakes. In Figure 6B, we mistakenly uploaded the repetitive images of group PCD70 as PCD40HEMA5, both N P=10 and 15. The corrected Figure 6B is shown below, the conclusion in the original remains unchanged. And we declare that there is no deliberate falsification of data in this research. , 
 ![file] , 
 The authors regret that in Figure 6B, the repetitive images of group PCD70 was mistakenly used instead of group PCD40HEMA5, both N P=10 and 15. We had send a draft corrigendum to the journal for publication. I would like to apologise for any inconvenience caused. The corrected Figure 6B is shown below. ![file] , 
 Thank you, Dr. Han and Dr. Dong, for correcting this figure. ,