Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Pneumoconiosis: current status and future prospects.

ABSTRACT: Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.

Facile synthesis of size controllable dendritic mesoporous silica nanoparticles.

The synthesis of highly uniform mesoporous silica nanospheres (MSNs) with dendritic pore channels, particularly ones with particle sizes below 200 nm, is extremely difficult and remains a grand challenge. By a combined synthetic strategy using imidazolium ionic liquids (ILs) with different alkyl lengths as cosurfactants and Pluronic F127 nonionic surfactants as inhibitors of particle growth, the preparation of dendritic MSNs with controlled diameter between 40 and 300 nm was successfully realized. An investigation of dendritic MSNs using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen physisorption revealed that the synthesis of dendritic MSNs at larger size (100-300 nm) strongly depends on the alkyl lengths of cationic imidazolium ILs; while the average size of dendritic MSNs can be controlled within the range of 40-100 nm by varying the amount of Pluronic F127. The Au@MSNs can be used as a catalyst for the reduction of 4-nitrophenol by NaBH4 into 4-aminophenol and exhibit excellent catalytic performance. The present discovery of the extended synthesis conditions offers reproducible, facile, and large-scale synthesis of the monodisperse spherical MSNs with precise size control and, thus, has vast prospects for future applications of ultrafine mesostructured nanoparticle materials in catalysis and biomedicine.