Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4

TY - JOUR

T1 - Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4

AU - Connor, Agnieszka J.

AU - Laskin, Jeffrey D.

AU - Laskin, Debra L.

N1 - Funding Information: Research described in this article was supported by NIH grants ES004738 , CA132634 , GM034310 , AR055073 , and ES005022 , and an Air Pollution Education and Research grant to AJC from the Mid-Atlantic States Section of the Air and Waste Management Association .

PY - 2012/4

Y1 - 2012/4

N2 - Inhalation of toxic doses of ozone is associated with a sterile inflammatory response characterized by an accumulation of macrophages in the lower lung which are activated to release cytotoxic/proinflammatory mediators that contribute to tissue injury. Toll-like receptor 4 (TLR4) is a pattern recognition receptor present on macrophages that has been implicated in sterile inflammatory responses. In the present studies we used TLR4 mutant C3H/HeJ mice to analyze the role of TLR4 in ozone-induced lung injury, oxidative stress and inflammation. Acute exposure of control C3H/HeOuJ mice to ozone (0.8. ppm for 3. h) resulted in increases in bronchoalveolar lavage (BAL) lipocalin 24p3 and 4-hydroxynonenal modified protein, markers of oxidative stress and lipid peroxidation. This was correlated with increases in BAL protein, as well as numbers of alveolar macrophages. Levels of surfactant protein-D, a pulmonary collectin known to regulate macrophage inflammatory responses, also increased in BAL following ozone inhalation. Ozone inhalation was associated with classical macrophage activation, as measured by increased NF-κB binding activity and expression of TNFα mRNA. The observation that these responses to ozone were not evident in TLR4 mutant C3H/HeJ mice demonstrates that functional TLR4 contributes to ozone-induced sterile inflammation and macrophage activation.

AB - Inhalation of toxic doses of ozone is associated with a sterile inflammatory response characterized by an accumulation of macrophages in the lower lung which are activated to release cytotoxic/proinflammatory mediators that contribute to tissue injury. Toll-like receptor 4 (TLR4) is a pattern recognition receptor present on macrophages that has been implicated in sterile inflammatory responses. In the present studies we used TLR4 mutant C3H/HeJ mice to analyze the role of TLR4 in ozone-induced lung injury, oxidative stress and inflammation. Acute exposure of control C3H/HeOuJ mice to ozone (0.8. ppm for 3. h) resulted in increases in bronchoalveolar lavage (BAL) lipocalin 24p3 and 4-hydroxynonenal modified protein, markers of oxidative stress and lipid peroxidation. This was correlated with increases in BAL protein, as well as numbers of alveolar macrophages. Levels of surfactant protein-D, a pulmonary collectin known to regulate macrophage inflammatory responses, also increased in BAL following ozone inhalation. Ozone inhalation was associated with classical macrophage activation, as measured by increased NF-κB binding activity and expression of TNFα mRNA. The observation that these responses to ozone were not evident in TLR4 mutant C3H/HeJ mice demonstrates that functional TLR4 contributes to ozone-induced sterile inflammation and macrophage activation.

KW - Macrophages

KW - NF-κB

KW - Ozone

KW - Sterile inflammation

KW - TLR4

KW - TNFα

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U2 - https://doi.org/10.1016/j.yexmp.2012.01.004

DO - https://doi.org/10.1016/j.yexmp.2012.01.004

M3 - Article

C2 - 22300504

VL - 92

SP - 229

EP - 235

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

SN - 0014-4800

IS - 2

ER -