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-kappaB 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-kappaB 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-alpha, 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.
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-kappaB 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-kappaB 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-alpha, 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.
Authors: Megan N Ballinger; Michael W Newstead; Xianying Zeng; Urvashi Bhan; Jeffrey C Horowitz; Bethany B Moore; David J Pinsky; Richard A Flavell; Theodore J Standiford Journal: J Immunol Date: 2012-06-01 Impact factor: 5.422
Authors: Barbara Rinaldi; Salvatore Cuzzocrea; Maria Donniacuo; Annalisa Capuano; Donatella Di Palma; Francesco Imperatore; Emanuela Mazzon; Rosanna Di Paola; Loredana Sodano; Francesco Rossi Journal: Intensive Care Med Date: 2011-05-13 Impact factor: 17.440
Authors: Akinori C Nagato; Frank S Bezerra; Manuella Lanzetti; Alan A Lopes; Marco Aurélio S Silva; Luís Cristóvão Porto; Samuel S Valença Journal: Int J Exp Pathol Date: 2012-08 Impact factor: 1.925