Role of Toll-like receptor 4 in hyperoxia-induced lung inflammation in mice

Y. Ogawa, S. Tasaka, Wakako Yamasawa, F. Saito, Naoki Hasegawa, T. Miyasho, A. Ishizaka

Research output: Contribution to journalArticle

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Abstract

Objective: Prolonged exposure to hyperoxia causes lung inflammation, but the role of Toll-like receptor 4 (TLR4) in hyperoxia-induced signal transduction remains unclear. Material or subjects: We evaluated neutrophil accumulation, signal transduction and cytokine production during hyperoxia, comparing TLR4 mutant (C3H/HeJ) and wild type (C3H/HeN) mice. Methods: The mice were exposed to 80% oxygen in a hyperoxic chamber for 0 (control), 48, or 96 h. After the exposure, bronchoalveolar lavage (BAL) was performed for differential cell counting and cytokine measurement. In lung homogenate, activation of NF-κB and STAT1 was also examined. Results: In C3H/HeJ mice, hyperoxia-induced neutrophil accumulation in BAL fluid was significantly decreased compared with C3H/HeN. Hyperoxia for 96 h caused NF-κB translocation in C3H/HeN mice, which was significantly attenuated in C3H/HeJ mice (p < 0.05). In contrast, STAT1 activation occurred as early as after 48 h of oxygen exposure, which did not differ between the two strains. The levels of TNF-α, IL-6, and KC in BAL fluid were increased after oxygen exposure, which was suppressed by the lack of TLR4 signaling. Conclusion: These results suggest that TLR4-dependent NF-kB activation may be an important process of the upregulation of proinflammatory mediators and subsequent neutrophil accumulation into the lung during hyperoxia.

Original languageEnglish
Pages (from-to)334-338
Number of pages5
JournalInflammation Research
Volume56
Issue number8
DOIs
Publication statusPublished - 2007 Aug

Fingerprint

Hyperoxia
Toll-Like Receptor 4
Pneumonia
Inbred C3H Mouse
Signal transduction
Chemical activation
Oxygen
Neutrophils
Bronchoalveolar Lavage Fluid
Cytokines
Fluids
NF-kappa B
Signal Transduction
Interleukin-6
Lung
Bronchoalveolar Lavage
Up-Regulation

Keywords

  • Hyperoxia
  • Neutrophils
  • NF-κB
  • Rodent
  • STAT1

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)
  • Immunology
  • Cell Biology

Cite this

Role of Toll-like receptor 4 in hyperoxia-induced lung inflammation in mice. / Ogawa, Y.; Tasaka, S.; Yamasawa, Wakako; Saito, F.; Hasegawa, Naoki; Miyasho, T.; Ishizaka, A.

In: Inflammation Research, Vol. 56, No. 8, 08.2007, p. 334-338.

Research output: Contribution to journalArticle

Ogawa, Y. ; Tasaka, S. ; Yamasawa, Wakako ; Saito, F. ; Hasegawa, Naoki ; Miyasho, T. ; Ishizaka, A. / Role of Toll-like receptor 4 in hyperoxia-induced lung inflammation in mice. In: Inflammation Research. 2007 ; Vol. 56, No. 8. pp. 334-338.
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