N-acetyl-L-cysteine inhibits bleomycin-induced interleukin-8 secretion by bronchial epithelial cells.
OBJECTIVE
Bleomycin (BLM) has proven effective for the treatment of cancers, but the most serious dose-limiting side-effect is the development of pulmonary toxicity. Although the precise mechanism in the pathogenesis of BLM-induced lung injury has not been determined, oxygen radicals and neutrophils are indicated to play a key role in it. Interleukin-8 (IL-8) is thought to be an important mediator of the pathogenesis of acute lung injury.


METHODS
The IL-8 production from bronchial epithelial cell line, BEAS-2B cells was measured by enzyme-linked immunosorbent assays for IL-8.


RESULTS
The concentrations of IL-8 were reportedly elevated in BLM-induced lung injury, suggesting the involvement of IL-8 in the pathogenesis of BLM-induced lung injury. In the present study, we showed that BLM induced the expression of IL-8 protein and mRNA in BEAS-2B cells, and N-acetyl-L-cysteine (NAC) inhibited IL-8 expression. In addition, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC) also effectively inhibited BLM-induced IL-8 production.


CONCLUSIONS
These results suggest that anti-oxidant-sensitive mechanism might be involved in the inhibition of IL-8 secretion by BLM-stimulated bronchial epithelial cells and that NAC might be useful for the treatment of BLM-induced lung injury.
Gon
Y
Y
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hashimoto
S
S
Nakayama
T
T
Matsumoto
K
K
Koura
T
T
Takeshita
I
I
Horie
T
T
D000111:Acetylcysteine / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D001761:Bleomycin / Q000009:adverse effects*; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000276:immunology* / Q000517:prevention & control; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D016166:Free Radical Scavengers; D016209:Interleukin-8; D011759:Pyrrolidines; D013859:Thiocarbamates; D001761:Bleomycin; C020972:pyrrolidine dithiocarbamic acid; D000111:Acetylcysteine