IMAMURA Y, YANAGIHARA K, SEKI M, OHNO H, MIYAZAKI Y, HIRAKATA Y, TOMONO K, TASHIRO T, KOHNO S; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. B-1522.
Nagasaki University School of Medicine, Nagasaki, Japan.
BACKGROUND: The feature of chronic air way disease including chronic bronchitis cystic fibrosis, bronchiectasis and diffuse panbronchitis are chronic bacterial infection and airway mucus obstruction. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection and the quorum-sensing systems contribute pathogenesis of this desease. The quorum-sensing signal molecules [N-(3-oxododecanoyl) homoserine lactone (3O-C[12]-HSL)] not only regulate bacterial virulence but also associate with immune response. In this study, we examed if 3O-C[12]-HSL could stimulate a major mucin core protein, MUC5AC production. We also studied inhibitory effect of macrolide on MUC5AC production. METHODS: The NCL-H292 epithelial cells were treated with 3O-C[12]-HSL. MUC5AC protein and mRNA were determined in the cells. Extracellular signal-regulated kinase (ERK)1/2 and I-kappaB phosphorylation were measured by western blots. RESULTS: 3O-C[12]-HSL induced epithelial cells to express MUC5AC at both the mRNA and protein levels in a dose-dependent manner. The increased ERK1/2 and I-kappaB phosphorylation were observed in the cells activated by 3O-C[12]-HSL. 3O-C[12]-HSL -induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. 15-memberd macrolide azithromycin also inhibited MUC5AC production activated by 3O-C[12]-HSL at both the mRNA and protein levels. CONCLUSIONS: These findings suggested that P. aeruginosa autoinducer 3O-C[12]-HSL contribute to excessive mucin production in chronic bacterial infection. And azithromycin reduced mucin production. As a result, azithromycin could reduce morbidity and mortality in these disease.
Publication Types:
Keywords:
- 4-Butyrolactone
- Anti-Bacterial Agents
- Azithromycin
- Cystic Fibrosis
- Epithelial Cells
- Mitogen-Activated Protein Kinases
- Mucins
- Pseudomonas aeruginosa
- Signal Transduction
- Transcription, Genetic
- Virulence
- genetics
- homoserine lactone
- mucin 5AC
Other ID:
UI: 102265284
From Meeting Abstracts