Expression of heme oxygenase in human airway epithelial cells.
Elevated levels of carbon monoxide (CO) are found in the exhaled breath of patients with inflammatory diseases such as asthma and cystic fibrosis. Endogenous CO is derived from heme oxygenase (HO) (EC 1.14.99.3), which catabolizes heme-producing CO and biliverdin. There are three isoforms of HO: HO-1 is inducible by inflammatory cytokines and oxidants, including nitric oxide (NO), whereas HO-2 and HO-3 are expressed constitutively. Primary airway epithelial cells were treated with either 50 ng/ml interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma (cytomix), or the NO donor NOC-18 for up to 24 h. Cytomix-induced HO-1 expression peaked at 4 h, returning to baseline by 24 h, whereas HO-2 expression remained unchanged. This increase in HO-1 expression could not be explained by an increase in NO production as inducible NO synthase expression increased between 12 and 24 h. However, the NO donor NOC-18 (500 microM) increased HO-1 expression twofold and HO activity 25-fold, whereas cytomix treatment increased HO activity eightfold. NO induction of HO-1 was not mediated via guanylyl cyclase and was not attenuated by 1 microM dexamethasone, although dexamethasone increased HO-2 protein. Therefore, airway epithelial cells express HO-2 and can express HO-1; thus, the epithelium may be a source of increased CO in airway diseases.
Department of Thoracic Medicine, Imperial College School of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom. l.donnelly@ic.ac.uk
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D000328:Adult; D001999:Bronchoscopy; D002470:Cell Survival; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008565:Membrane Proteins; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; C484584:heme oxygenase-3 protein, human; D019331:NG-Nitroarginine Methyl Ester