IRF3 and IRF7 contribute to diesel exhaust particles-induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice
Abstract
Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the interferon response factors IRF3 and IRF7 played pivotal roles in DEP-induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP-induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR-independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters. This article is protected by copyright. All rights reserved.
References
Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon
Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model
DNA-binding landscape of IRF3, IRF5 and IRF7 dimers: implications for dimer-specific gene regulation
Citations
Related Concepts
Related Feeds
Autophagy & Disease
Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.
Autophagy & Model Organisms
Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms