Endotoxin-induced lung injury in α-galactosylceramide-sensitized mice is caused by failure of interleukin-4 production in lung natural killer T cells

J. Dagvadorj, G. Tumurkhuu, Y. Naiki, A. S.M. Noman, I. Iftakhar-E-Khuda, B. Badamtseren, T. Komatsu, N. Koide, T. Yoshida, T. Yokochi

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4 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalClinical and Experimental Immunology
Volume162
Issue number1
DOIs
Publication statusPublished - 10-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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