Inflammasome-Independent Leukotriene B₄ Production Drives Crystalline Silica-Induced Sterile Inflammation.

ABSTRACT: Silicosis is a lung inflammatory disease caused by chronic exposure to crystalline silica (CS). Leukotriene B₄ (LTB₄) plays an important role in neutrophilic inflammation, which drives silicosis and promotes lung cancer. In this study, we examined the mechanisms involved in CS-induced inflammatory pathways. Phagocytosis of CS particles is essential for the production of LTB₄ and IL-1β in mouse macrophages, mast cells, and neutrophils. Phagosomes enclosing CS particles trigger the assembly of lipidosome in the cytoplasm, which is likely the primary source of CS-induced LTB₄ production. Activation of the JNK pathway is essential for both CS-induced LTB₄ and IL-1β production. Studies with bafilomycin-A1- and NLRP3-deficient mice revealed

SUBMITTER: Hegde B 

PROVIDER: S-EPMC5940517 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature