Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-alpha following ozone inhalation.

Toxicology and Applied Pharmacology
Ladan FakhrzadehDebra L Laskin

Abstract

Alveolar macrophages (AM) and inflammatory mediators including nitric oxide and peroxynitrite contribute to ozone-induced lung injury. The generation of these mediators is regulated, in part, by the transcription factor NF-kappaB. We previously demonstrated a critical role for NF-kappaB p50 in ozone-induced injury. In the present studies mechanisms regulating NF-kappaB activation in the lung after ozone inhalation were analyzed. Treatment of wild type (WT) mice with ozone (0.8 ppm, 3 h) resulted in a rapid increase in NF-kappaB binding activity in AM, which persisted for at least 12 h. This was not evident in mice lacking TNFalpha which are protected from ozone-induced injury; there was also no evidence of nitric oxide or peroxynitrite production in lungs from these animals. These data demonstrate that TNFalpha plays a role in NF-kappaB activation and toxicity. TNFalpha signaling involves PI-3-kinase (PI3K)/protein kinase B (PKB), and p44/42 MAP kinase (MAPK) which are important in NF-kappaB activation. Ozone Inhalation resulted in rapid and transient increases in p44/42 MAPK and PI3K/PKB in AM from WT mice, which was evident immediately after exposure. Caveolin-1, a transmembrane protein that negatively regulates PI3K/PKB and ...Continue Reading

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Citations

Oct 5, 2010·Annual Review of Pharmacology and Toxicology·Debra L LaskinJeffrey D Laskin
Jun 16, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Marsha P Cole, Bruce A Freeman
Aug 7, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ruth A RobertsWilliam Slikker
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Jul 3, 2015·The Journal of Investigative Dermatology·Yukie YamaguchiMichiko Aihara
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Jun 24, 2017·Pharmacology & Therapeutics·Rama MalaviyaDebra L Laskin
Aug 19, 2010·Annals of the New York Academy of Sciences·Debra L LaskinJeffrey D Laskin
May 28, 2020·Critical Reviews in Toxicology·Sonika Patial, Yogesh Saini
Sep 29, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mary FrancisDebra L Laskin
Jun 2, 2009·Biological & Pharmaceutical Bulletin·Sung-Hwa SohnHyunsu Bae
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Oct 31, 2020·Pathogens·Bikash Sahay, Ayalew Mergia
Sep 25, 2021·Physiological Reports·Gregory J SmithSamir N P Kelada

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