title: Endotoxin-induced lung injury in α-galactosylceramide-sensitized mice is caused by failure of interleukin-4 production in lung natural killer T cells.
abstract: Administration of bacterial lipopolysaccharide (LPS) known as endotoxin into α-galactosylceramide (α-GalCer)-sensitized mice causes severe lung lesions but few hepatic lesions in lethal shock, and interferon (IFN)-γ is suggested to play a pivotal role in preparation of the lung lesions. In order to clarify the mechanism of how α-GalCer sensitization causes lung lesions exclusively in mice, we examined the differential responsiveness of lungs and livers to α-GalCer sensitization. Although lung and liver natural killer T (NK T) cells both produced IFN-γ in response to α-GalCer, IFN-γ signalling was triggered only in the lungs of α-GalCer-sensitized mice. Lung NK T cells did not produce interleukin (IL)-4 in response to α-GalCer and it did not induce the expression of suppressor of cytokine signalling 1 (SOCS1) in the lungs. Conversely, IL-4 produced by liver NK T cells led to the expression of SOCS1 in the livers of the mice. Neutralization of IL-4 reduced SOCS1 expression in the livers and exacerbated LPS-induced hepatic lesions. IL-10 was produced by liver NK T cells but not lung NK T cells. However, IL-10 was produced constitutively by alveolar epithelial cells in normal lung. Lung NK T cells and liver NK T cells might express CD8 and CD4, respectively. Based on the fact that IL-4 inhibited IFN-γ signalling in the livers of α-GalCer-sensitized mice via SOCS1 expression and signal transducer and activator of transcription 1 (STAT-1) activation, no inhibition of the IFN-γ signalling in the lungs caused LPS-induced lung lesions in α-GalCer-sensitized mice. The detailed mechanism of development of the lung lesions in α-GalCer-sensitized mice is discussed.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Dagvadorj
authors.forename: G
authors.initials: G
authors.lastname: Tumurkhuu
authors.forename: Y
authors.initials: Y
authors.lastname: Naiki
authors.forename: A S M
authors.initials: AS
authors.lastname: Noman
authors.forename: I
authors.initials: I
authors.lastname: Iftakhar-E-Khuda
authors.forename: B
authors.initials: B
authors.lastname: Badamtseren
authors.forename: T
authors.initials: T
authors.lastname: Komatsu
authors.forename: N
authors.initials: N
authors.lastname: Koide
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004731:Endotoxins / Q000633:toxicity; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology*; D015151:Immunoblotting; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D004731:Endotoxins; D005699:Galactosylceramides; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C493154:alpha-galactosylceramide; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma