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OBJECTIVE: To study the mechanism of tumor necrosis factor( TNF)-α and its receptor( TNFR) signal transduction pathways in regulating cell apoptosis of alveolar macrophage( AM) in coal workers' pneumoconiosis( CWP).METHODS: Twenty-four coal workers with pneumoconiosis at stage Ⅰ were selected as CWP group and four observation subjects exposed to coal were chosen as observation group by using simple random sampling method. The bronchoalveolar lavage fluids of whole-lung lavage of two groups were collected. AMs were separated and purified. Then they were divided into 6 groups: a control group,a superoxide dismutase( SOD) group,a TNF/TNFR group,an anti-TNF-α antibody group,a Caspase-8 suppression group and a nuclear factor-κB( NF-κB) suppression group. The AMs of 6 groups with corresponding treatment were cultivated. After 24 hours,the cells were harvested and proteins extracted. The relative expression of TNF-α,TNFR1,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 protein was detected by Western blotting. RESULTS: The protein relative expression of TNF-α,TNFR2,Caspase-8,Caspase-3,NF-κB P50 and NF-κB P65 in CWP group was significantly higher than those in the observation group( P < 0. 05). The protein relative expression of TNF-α,TNFR1,Caspase-8,Caspase-3 and NF-κB P50 in the TNF/TNFR group and the anti-TNF-αantibody group was lower than that of the control group( P < 0. 05). The above indexes in the anti-TNF-α antibody group were lower than that of the NF-κB suppression group( P < 0. 05). The protein relative expression of TNFR1,Caspase-8and Caspase-3 in the TNF/TNFR group was higher than that of the SOD group and the Caspase-8 suppression group( P <0. 05). The protein relative expression of TNFR1,Caspase-8 and NF-κB P50 in the TNF/TNFR group was lower than that of the NF-κB suppression group( P < 0. 05). Among the CWP patients,the relative expression of TNFR2 and NF-κB P65 in the TNF/TNFR group was lower than that of the control group( P < 0. 05),and higher than that of the SOD group( P <0. 05). CONCLUSION: AM apoptosis mediated by TNF-α/TNFR/NF-κB signal transduction pathway plays an important role in the occurrence and development of CWP. The TNF-α/TNFR/NF-κB signal transduction pathways inhibited or blocked at different stages can affect the expression of proteins related to AM apoptosis.
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Objective To investigate the relationship between serum levels of surfactant protein( SP)-A,SP-C and lung function impairment in coal workers with pneumoconiosis(CWP) in order to provide evidence for the biomarker study of pneumoconiosis.Methods Thirty-two coal workers with pneumoconiosis snd 41 healthy controls were included in this study.Serum levels of SP-A and SP-C were measured.Grading assessment of dyspnea and pulmonary function including predicted percentages of FVC,FEV1,FEV/FVC,MVV,and DLCO were conducted.Results Among the 32 participants with CWP,the severity of dyspnea was rated as level Ⅲ for 14 and level Ⅳ for 18 individuals.The pulmonary function was significantly impaired in CWP patients with level Ⅳ dyspnea compared with the healthy controls (FEV1％ predicted:[69.38 ± 15.17 ]％ vs.[96.35 ±10.24 ] ％ ; MVV％ predicted:[ 65.89± 8.14 ] ％ vs.[ 94.13 ± 10.38 ] ％ ; DLCO％ predicted:[ 96.51 ±11.37 ] ％.The serum levels of SP-A and SP-C were significantly higher in CWP patients than that in the healthy controls (SP-A:[4.02 ± 1.22] μg/L vs.[2.41 ±0.68 ] μg/L,t =6.480,P =0.001 ;SP-C:[3.58 ±0.67 ] ng/L vs.[ 2.31 ± 0.29] ng/L,t =9.290,P ＜ 0.001 ).Serum SP-A and SP-C levels in CWP patients were found to be significantly correlated with exposure to dust,dyspnea severity,FEV1％ predicted and DLCO％ predicted.Conclusion Serum SP-A and SP-C levels in CWP patients are closely associated with lung function,suggesting their role as candidate biomarkers for CWP.