A potent inhibitor of cytosolic phospholipase A2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice

Acute respiratory distress syndrome (ARDS) is an acute lung injury of high mortality rate, and sepsis syndrome is one of the most frequent causes of ARDS. Metabolites of arachidonic acid, including thromboxanes and leukotrienes, are proinflammatory mediators and potentially involved in the developme...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2003-05, Vol.28 (5), p.L720-L726
Main Authors: NAGASE, Takahide, UOZUMI, Naonori, AOKI-NAGASE, Tomoko, TERAWAKI, Kan, ISHII, Satoshi, TOMITA, Tetsuji, YAMAMOTO, Hiroshi, HASHIZUME, Kohei, OUCHI, Yasuyoshi, SHIMIZU, Takao
Format: Article
Language:English
Subjects:
Bacterial diseases
Biological and medical sciences
Cytokines
Experimental bacterial diseases and models
Infectious diseases
Injuries
Lungs
Medical sciences
Phosphorus
Rodents
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Summary:Acute respiratory distress syndrome (ARDS) is an acute lung injury of high mortality rate, and sepsis syndrome is one of the most frequent causes of ARDS. Metabolites of arachidonic acid, including thromboxanes and leukotrienes, are proinflammatory mediators and potentially involved in the development of ARDS. A key enzyme for the production of these inflammatory mediators is cytosolic phospholipase A2 (cPLA2). Recently, it has been reported that arachidonyl trifluoromethyl ketone (ATK) is a potent inhibitor of cPLA2. In the present study, we hypothesized that pharmacological intervention of cPLA2 could affect acute lung injury. To test this hypothesis, we examined the effects of ATK in a murine model of acute lung injury induced by septic syndrome. The treatment with ATK significantly attenuated lung injury, polymorphonuclear neutrophil sequestration, and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. The current observations suggest that pharmacological intervention of cPLA2 could be a novel therapeutic approach to acute lung injury caused by sepsis syndrome. [PUBLICATION ABSTRACT]
ISSN:1040-0605
1522-1504