Suppression of oxidant-induced glutathione synthesis by erythromycin in human bronchial epithelial cells. 2008

Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical College, Guangzhou, PR China.

BACKGROUND Macrolide antibiotics have anti-inflammatory effects which are utilized for the treatment of chronic inflammatory airway diseases. Recently, their anti-inflammatory effects have been proposed to be beneficial in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE Since the molecular mechanisms of anti-inflammatory effects are associated with inhibition of activator protein 1 (AP-1) and nuclear factor (NF)-kappaB, and both are reported to be involved in the expression of gamma-glutamylcysteine synthetase (gamma-GCS), we set out to determine if these drugs influence the oxidant-antioxidant balance in human bronchial epithelial (HBE) cells. METHODS 16HBE cells were preincubated with erythromycin (EM) at different concentrations and times and then exposed to hydrogen peroxide (0.01 mM). Levels of interleukin (IL)-8 and glutathione (GSH), and activity of gamma-GCS and gamma-GCS heavy subunit (gamma-GCS-HS) protein production were assayed. AP-1 and NF-kappaB binding to the 5'-flanking region of IL-8 and gamma-GCS-HS genes was assessed by electrophoretic mobility-shift assay. RESULTS The increase in IL-8 levels and activity of AP-1 induced by H(2)O(2) were abrogated by preincubation of the cells with EM (5 mug/ml) for 36 h. We also showed that preincubation with EM for 48 h inhibited H(2)O(2)-induced GSH levels, gamma-GCS activity and expression of gamma-GCS-HS, and decreased AP-1 binding to the gamma-GCS-HS 5'-flanking region. CONCLUSIONS The confirmation of antioxidants maintaining enzyme suppression by EM raised concerns on whether this drug could disrupt the oxidant/ antioxidant balance during long-term use. These data provide important insights into the treatment of inflammatory lung diseases with macrolide antibiotics.

UI MeSH Term Description Entries
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D004917 Erythromycin A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Erycette,Erymax,Erythromycin A,Erythromycin C,Erythromycin Lactate,Erythromycin Phosphate,Ilotycin,T-Stat,Lactate, Erythromycin,Phosphate, Erythromycin,T Stat,TStat
D005721 Glutamate-Cysteine Ligase One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2. gamma-Glutamyl-Cysteine Synthetase,Glutamylcysteine Synthetase,Glutamate Cysteine Ligase,Ligase, Glutamate-Cysteine,Synthetase, Glutamylcysteine,Synthetase, gamma-Glutamyl-Cysteine,gamma Glutamyl Cysteine Synthetase
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D016209 Interleukin-8 A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. CXCL8 Chemokine,Chemokine CXCL8,Chemotactic Factor, Macrophage-Derived,Chemotactic Factor, Neutrophil, Monocyte-Derived,IL-8,Neutrophil-Activating Peptide, Lymphocyte-Derived,Neutrophil-Activating Peptide, Monocyte-Derived,AMCF-I,Alveolar Macrophage Chemotactic Factor-I,Anionic Neutrophil-Activating Peptide,Chemokines, CXCL8,Chemotactic Factor, Neutrophil,Granulocyte Chemotactic Peptide-Interleukin-8,IL8,Monocyte-Derived Neutrophil Chemotactic Factor,Neutrophil Activation Factor,Alveolar Macrophage Chemotactic Factor I,Anionic Neutrophil Activating Peptide,CXCL8 Chemokines,CXCL8, Chemokine,Chemokine, CXCL8,Chemotactic Factor, Macrophage Derived,Chemotactic Peptide-Interleukin-8, Granulocyte,Granulocyte Chemotactic Peptide Interleukin 8,Interleukin 8,Lymphocyte-Derived Neutrophil-Activating Peptide,Macrophage-Derived Chemotactic Factor,Monocyte-Derived Neutrophil-Activating Peptide,Neutrophil Activating Peptide, Lymphocyte Derived,Neutrophil Activating Peptide, Monocyte Derived,Neutrophil Chemotactic Factor,Neutrophil-Activating Peptide, Anionic,Peptide, Anionic Neutrophil-Activating

Related Publications

Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
April 2005, Zhonghua yi xue za zhi,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
January 2014, Thorax,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
April 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
October 1994, Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
July 1998, The European respiratory journal,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
January 2001, Current protocols in toxicology,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
August 2011, Zhonghua yi xue za zhi,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
January 2017, Allergology international : official journal of the Japanese Society of Allergology,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
March 2009, Experimental lung research,
Zhiyi He, and Bing Li, and Liang Yu, and Qicai Liu, and Nanshan Zhong, and Pixin Ran
July 1997, American journal of respiratory and critical care medicine,
Copied contents to your clipboard!