Objective: To investigate the expression and significance of NLRP3/IL-1β/TGF-β₁ signal axis in a rat model of silicosis and pulmonary fibrosis. Methods: Eighty healthy Wistar male rats of SPF grade were randomly divided into 4 groups: high (100 mg/ml) , medium (50 mg/ml) , low (25 mg/ml) concentration SiO₂ dusting group and normal negative control. Group, 20 in each group. Five rats were sacrificed at 7 d, 14 d, 28 d and 56 d after SiO₂ dusting. The degree of alveolitis and the degree of pulmonary fibrosis were observed. The enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β in lung tissue. The expressions of NLRP3 and Caspase-1 in lung tissue of rats were detected by Western Blot. Results: The alveolitis score and fibrosis degree of the rats in the dust-receiving group were significantly higher than those in the control group at 7 d, 14 d, 28 d and 56 d, and the difference was statistically significant (P<0.01) . The concentrations of IL-1β, IL-18 and TGF-β1 in 14 d, 28 d and 56 d were significantly higher than those in the control group (P<0.01) . The expressions of NLRP3 and Caspase-1 in lung tissue of rats exposed to dust were 7 d and 14 d, 28 d, 56d were higher than the control group (P<0.01) ; the expression levels of NLRP3, Caspase-1, IL-1β, IL-18 and TGF-β₁ in the low, medium and high concentration SiO₂ dusting group were 7 d, 14 d and The difference between the two groups was statistically significant (P<0.05) , and both showed a time-effect relationship with the increase of dusting time. Conclusion NLRP3 and its downstream factors Caspase-1, IL-1β, IL-18 and TGF-β1 are highly expressed in the lung tissue of rats with silicosis and pulmonary fibrosis, suggesting that the NLRP3/IL-1β/TGF-β₁ signal axis may be associated with silicosis. Pulmonary fibrosis has a close relationship and plays a role in the formation of silicosis.

OBJECTIVE: To investigate the mechanism of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3( NLRP3) inflammasome in the development and progression of silicosis pulmonary fibrosis,and to explore the effect of NLRP3 inhibitor MCC950 on silicosis pulmonary fibrosis. METHODS: The specific pathogen free Wistar male rats were randomly divided into control group,model group and inhibitor group,with 20 rats in each group.The rats in the model group and the inhibitor group were given a 1. 0 m L of free silica suspension at a concentration of 50 g/L by the non-exposure endotracheal intubation method. Rats in the control group were given an equal volume of sterilized 0. 9% sodium chloride solution. Rats in the inhibitor group were given 10 mg/kg body weight of MCC950 once every other day by gavage,while rats in the model group and the control group were given an equal volume of sterilized0. 9% sodium chloride solution. Five rats were randomly sacrificed at 7,14,28,and 56 days after model establishment.The body weight of the rats was weighed,and the degree of pulmonary alveolitis and pulmonary fibrosis was observed. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin( IL)-1β,IL-18 and transforming growth factor-β1( TGF-β1) of lung tissues. Western blotting was used to detect the relative expression of NLRP3 and Caspase-1protein. RESULTS: The body mass of rats increased with increasing observation time( P < 0. 01). The scores of pulmonary fibrosis and the levels of IL-1β,IL-18 and TGF-β1 in lung tissue had statistical significance in the main effect of dust treatment( P < 0. 01),and the order from high to low was model group,inhibitor group and control group( P < 0. 01). At the time points of 7,14,28,and 56 days after model establishment,the score of pulmonary alveolitis and the relative expression of NLRP3 and Caspase-1 protein in lung tissues in the inhibitor group were lower than that of the model group( P < 0. 01),but higher than that of the control group( P < 0. 01). CONCLUSION: The NLRP3/IL-1β/TGF-β1 signaling pathway plays an important role in the development of silicosis pulmonary fibrosis. MCC950 can inhibit the development and progression of pulmonary fibrosis of silicosis by inhibiting the activation of NLRP3 inflammasome.

Objective: To observe serum levels of periostin, ECP, IgE in the antibiotic enterprise workers, and study the role of periostin, ECP, IgE in the development of allergic inflammation. Methods: 90 cases with asthma or rhinitis were enrolled as disease group, another 117 workers exposed to 7-ACA、6-APA dust without suffering from allergic illness, are chosen as group of dust exposed, and 192 healthy workers who didn’t contact dust were chosen as control group. Questionnaires were used to learn their basic information.Lung function was determined with a portable spirometer.The expression levels of periostin、ECP and IgE in serum were measured by enzyme-linked immuno sorbent assay. Results: The exposure group and disease group had significantly lower forced vital capacity (FVC) , forced expiratory volume in 1 second (FEV_l.0) , and FEV_l.0/FVC ratio than the control group (P<0.05) . The disease group had significantly higher eosinophil than the control group (P<0.05) . Compared with the control group, the exposure group, the disease group, asthma subgroup, rhinitis subgroup of serum periostin and IgE increased, the differences are statistically significant (P<0.05) . Serum levels of ECP in the workers of asthma subgroup were significantly higher than that in control group (P<0.05) . Serum expression levels of periostin were positively correlated with IgE, ECP in workers (P<0.001) , serum levels of periostin were negatively correlated with FEV_1.0 in workers (P<0.05) . Multiple logistics regression analysis found that exposure to 7-ACA or 6-APA (OR=3.09, 95%CI: 1.83-5.21) , age>47years (OR=2.53, 95%CI: 1.22-5.26) , higher ECP (OR=1.04, 95%CI: 1.01-1.06) were risk factors for increased serum periostin level. Conclusion Occupational exposure to 7-ACA or 6-APA can result in higher serum periostin level, exposure to 7-ACA or 6-APA, age>47 years, higher ECP are risk factors for increased serum periostin level.