Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice. Issue 3 (September 2016)

• Record Type: Journal Article
• Authors: Wu, Dongdong; Pan, Pinhua; Su, Xiaoli; Zhang, Lemeng; Qin, Qingwu; Tan, Hongyi; Huang, Li; Li, Yuanyuan
• Is Part Of: Shock. Volume 46:Issue 3(2016:Sep.)
• Publication Date: 2016-09
• Subjects: Acute lung injury -- alveolar macrophage -- caspase-1 -- interferon regulatory factor-1 -- pyroptosis -- ALI -- acute lung injury -- AMs -- alveolar macrophages -- ARDS -- acute respiratory distress syndrome -- ASC -- apoptosis-associated speck-like protein containing a caspase activation and recruitment domain -- ATP -- adenosine triphosphate -- BALF -- bronchoalveolar lavage fluid -- HMGB1 -- high-mobility group box 1 -- IFN -- interferon -- IRF-1 -- interferon regulatory factor 1 -- KO -- knockout -- LDH -- Lactate dehydrogenase -- LPS -- lipopolysaccharide -- MyD88 -- myeloid differentiation factor 88 -- NLRP3 -- nod-like receptor protein 3 -- PAMP -- pathogen-associated molecular pattern -- qPCR -- quantitative PCR -- TLR-4 -- toll-like receptor 4 -- WT -- wild-type; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000595
• Languages: English
• ISSNs: 1073-2322

Abstract

Abstract : ABSTRACT: Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation.