In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation.

Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW
J Immunol. 1996 157 (4): 1630-7

PMID: 8759749

We hypothesized that endotoxin injection in rats would stimulate in vivo nuclear factor-kappa B (NF-kappa B) activation in lung tissue and that antioxidant treatment before endotoxin injection would attenuate endotoxin-induced NF-kappa B activation, chemokine gene expression, and neutrophilic lung inflammation. We studied NF-kappa B activation in rat lung tissue following a single i.p. injection of endotoxin (6 mg/kg). After in vivo endotoxin treatment, lung NF-kappa B activation peaked at 2 h and temporally correlated with the expression of cytokine-induced neutrophil chemoattractant mRNA in lung tissue. Treatment with the antioxidant N-acetylcysteine (NAC) 1 h before endotoxin resulted in decreased lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and diminished cytokine-induced neutrophil chemoattractant mRNA expression in lung tissue. Treatment with NAC significantly suppressed endotoxin-induced neutrophilic alveolitis. The average total lung lavage neutrophil count was 5.5 x 10(6) with endotoxin treatment vs 0.9 x 10(6) with NAC treatment before endotoxin. The NF-kappa B pathway represents an attractive therapeutic target for strategies to control neutrophilic inflammation and lung injury.

MeSH Terms (30)

Acetylcysteine Animals Anti-Inflammatory Agents, Non-Steroidal Antioxidants Base Sequence Chemokines, CXC Chemotactic Factors Chemotaxis, Leukocyte Dinoprost Disease Models, Animal Drug Evaluation, Preclinical Endotoxins F2-Isoprostanes Gene Expression Regulation Glutathione Growth Substances Inflammation Intercellular Signaling Peptides and Proteins Leukocyte Count Lung Lung Diseases Male Molecular Sequence Data Neutrophils NF-kappa B Rats Rats, Sprague-Dawley Respiratory Distress Syndrome, Adult RNA, Messenger Sepsis

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