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

Y. Ogawa, S. Tasaka, W. Yamada, F. Saito, N. Hasegawa, T. Miyasho, A. Ishizaka

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 1

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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