Ergothioneine inhibits oxidative stress- and TNF-alpha-induced NF-kappa B activation and interleukin-8 release in alveolar epithelial cells.
Oxidants and inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha) activate transcription factors such as NF-kappa B. Interleukin-8 (IL-8) is a ubiquitous inflammatory chemokine that mediates a multitude of inflammatory events in the lung. Ergothioneine is a naturally occurring thiol compound, which possesses antioxidant property. The aim of this study was to determine whether ergothioneine can inhibit the hydrogen peroxide (H(2)O(2))- and TNF-alpha-mediated activation of NF-kappa B and the release of IL-8 in human alveolar epithelial cells (A549). Treatment of A549 cells with H(2)O(2) (100 microM) and TNF-alpha (10 ng/ml) significantly increased NF-kappa B activation using a reporter assay. Ergothioneine inhibited both H(2)O(2)- and TNF-alpha-mediated activation of NF-kappa B. Both H(2)O(2) and TNF-alpha significantly increased IL-8 release, which was inhibited by pre-treatment of A549 cells with ergothioneine compared to the control untreated cells. Ergothioneine also abolished the transcriptional activation of IL-8 in an IL-8-chloramphenicol acetyltransferase (CAT) reporter system, transfected into A549 cells. This indicates a molecular mechanism for the anti-inflammatory effects of ergothioneine.
Rahman
Irfan
I
ELEGI and Colt Research Laboratory, Respiratory Medicine Unit, Wilkie Building, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK. irfan.rahman@ed.ac.uk
Gilmour
Peter S
PS
Jimenez
Luis A
LA
Biswas
Saibal K
SK
Antonicelli
Frank
F
Aruoma
Okezie I
OI
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004880:Ergothioneine / Q000378:metabolism / Q000494:pharmacology*; D017930:Genes, Reporter; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000975:Antioxidants; D016209:Interleukin-8; D016328:NF-kappa B; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D004880:Ergothioneine; D005978:Glutathione