Expression and significance of NLRP3/IL-1β/TGF-β(1) signal axis in rat model of silicosis pulmonary fibrosis

Objective: To investigate the expression and significance of NLRP3/IL-1β/TGF-β(1) 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 SiO(2) 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 SiO(2) 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-β(1) in the low, medium and high concentration SiO(2) 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-β(1) signal axis may be associated with silicosis. Pulmonary fibrosis has a close relationship and plays a role in the formation of silicosis.