Inflammation and the regulation of glutathione level in lung epithelial cells.
Inflammation is a highly complex biochemical protective response to cellular injury. If this process is continuously unchecked, it leads to chronic inflammation, a hallmark of various inflammatory lung diseases. Reactive oxygen intermediates generated by immune cells recruited to the sites of inflammation are a major cause of cell damage. Glutathione (GSH), is a vital intra- and extracellular protective antioxidant in the lungs. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). Both GSH and gamma-GCS expression are modulated by oxidants, phenolic antioxidants, inflammatory, and anti-inflammatory agents in lung cells. GSH plays a key role in regulating oxidant-induced lung epithelial cell function and also in the control of pro-inflammatory processes. Alterations in the alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases. Oxidative processes have a fundamental role in lung inflammation through redox-sensitive transcription factors such as NF-kappaB and AP-1, which regulated the genes for pro-inflammatory mediators and protective antioxidant genes such as gamma-GCS. The critical balance between the induction of pro-inflammatory mediators and antioxidant genes in response to oxidative stress at the site of inflammation is not known. Knowledge of the mechanisms of GSH regulation in lung inflammation could lead to the development of novel therapies based on the pharmacological manipulation of the production of this important antioxidant in lung inflammation and injury. This review describes the potential role of GSH for lung oxidant stress, inflammation and injury.
Rahman
I
I
Department of Respiratory Medicine, University of Edinburgh, Medical School, UK. ir@srv1.med.ed.ac.uk
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D016877:Oxidants / Q000009:adverse effects; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000975:Antioxidants; D018836:Inflammation Mediators; D016877:Oxidants; D013438:Sulfhydryl Compounds; D014157:Transcription Factors; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione