title: Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury.
abstract: Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS). Our previous data indicates that ASK1 plays a pivotal role in hyperoxia-induced acute lung injury (HALI). However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. In this study, we investigated whether ASK1 deletion would lead to attenuation of HALI. Our results show that ASK1 deletion in vivo significantly suppresses hyperoxia-induced elevation of inflammatory cytokines (i.e. IL-1β and TNF-α), cell apoptosis in the lung, and recruitment of immune cells. In summary, the results from the study suggest that deletion of ASK1 in mice significantly inhibits hyperoxic lung injury.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Jutaro
authors.initials: J
authors.lastname: Fukumoto
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.|Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Ruan
authors.initials: R
authors.lastname: Cox
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Fukumoto
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Young
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Prasanna Tamarapu
authors.initials: PT
authors.lastname: Parthasarathy
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Galam
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Narasaiah
authors.initials: N
authors.lastname: Kolliputi
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D018496:Hyperoxia / Q000150:complications* / Q000235:genetics / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse