title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice.
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.
authors.affiliation: *Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China †Department of Thoracic Medicine, Hunan Cancer Hospital, Affiliated to Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wu
authors.forename: Pinhua
authors.initials: P
authors.lastname: Pan
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Su
authors.forename: Lemeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Qin
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D024243:HMGB1 Protein / Q000097:blood; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000069292:Pyroptosis / Q000235:genetics / Q000502:physiology*
chemical_list: D024243:HMGB1 Protein; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18; D053583:Interleukin-1beta; D008070:Lipopolysaccharides