N-acetylcysteine inhibits IL-1 alpha-induced IL-8 secretion by bronchial epithelial cells.
The protective effects of N-acetylcysteine (NAC) have been documented in experimental and clinical acute lung injury. However, the effect of NAC on the secretion of interleukin-8-(IL-8), which is an important mediator of the pathogenesis of acute lung injury through the recruitment of neutrophils, has not been determined. In the present study, therefore, we examined the effect of NAC on IL-8 secretion by IL-1 alpha-stimulated bronchial epithelial cells. NAC inhibited IL-8 secretion by bronchial epithelial cells in a dose-dependent manner. In addition, the structurally unrelated antioxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC) also effectively inhibited secretion. These results indicated that an antioxidant-sensitive mechanism might be involved in inhibition of IL-8 secretion by IL-1 alpha-stimulated bronchial epithelial cells. The protective effects of NAC on acute lung injury have been suggested to be due to scavenging reactive oxygen intermediates (ROIs) and stimulation of glutathione synthesis. In addition to this, our results may provide an alternative explanation for the efficacy of NAC on acute lung injury.
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
K
K
Matsumoto
S
S
Hashimoto
Y
Y
Gon
T
T
Nakayama
H
H
Takizawa
T
T
Horie
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D007375:Interleukin-1; D016209:Interleukin-8; D011759:Pyrrolidines; D013859:Thiocarbamates; D002083:Butylated Hydroxyanisole; C020972:pyrrolidine dithiocarbamic acid; D000111:Acetylcysteine