NF-kappa B mediates silica-induced pulmonary inflammation by promoting the release of IL-1 beta in macrophages

Long-term exposure to respirable silica particles causes pulmonary inflammation and fibrosis primarily promoted by cytokines released from alveolar macrophages, yet the underlying mechanism is still unclear. From the perspective of nuclear factor kappa B (NE-kappa B), we studied the mechanism of IL-1 beta biosynthesis and release. Utilizing BAY 11-7082, an NF-kappa B specific inhibitor, we showed the alteration of macrophage viability and examined the expression of both IL-1 beta and NF-kappa B in vitro. We found that silica nanoparticles (SiNPs) were internalized by macrophages and caused damage to cell integrity. The immunofluorescence assay showed that SiNPs exposure enhanced the expression of IL-1 beta and NE-kappa B, which could be effectively suppressed by BAY 11-7082. Besides, we built silica exposure mouse model by intratracheally instilling 5 mg of SiNPs and checked the effect of silica exposure on pulmonary pathological changes. Consistently, we found an upregulation of IL-1 beta and NF-kappa B after SiNPs exposure, along with the aggravated inflammatory cell infiltration, thickened alveolar wall, and enhanced expression of collagens. In conclusion, SiNPs exposure causes pulmonary inflammation and fibrosis that is regulated by NK-kappa B through upregulating IL-1 beta in alveolar macrophages.