The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells.
- Author:
Chang Hoon BAE
1
;
Seung Min CHEN
;
Heung Man LEE
;
Si Youn SONG
;
Yong Dae KIM
Author Information
1. Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea. ydkim@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Doxycycline;
Inflammation;
Phorbol myristate acetate;
Matrix metalloproteinase-9;
p38;
Mucins;
MUC5B;
Epithelial cells;
NCI-H292 cell
- MeSH:
Blotting, Western;
Doxycycline;
Epithelial Cells;
Gelatin;
Humans;
Immunoenzyme Techniques;
Inflammation;
Matrix Metalloproteinase 9;
Mucins;
Phorbols;
Phosphorylation;
Protein Kinase C;
RNA, Messenger;
Signal Transduction;
Tetradecanoylphorbol Acetate;
Thiram
- From:Clinical and Experimental Otorhinolaryngology
2011;4(4):177-183
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVES: Doxycycline is commonly used in medicine for its bacteriostatic antimicrobial properties. Recent studies have reported that doxycycline also has anti-inflammatory effects. Matrix metalloproteinase (MMP)-9 has been found to be involved in the physiological and pathological process of inflammatory airway disease. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, is known to stimulate the expression of MMP and mucin genes in the airway and intestinal epithelial cells. Therefore, the effects and signal pathways of doxycycline on PMA-induced MUC5B expression dependent MMP-9 in human airway epithelial cells were investigated. METHODS: In human NCI-H292 airway epithelial cells, MUC5B and MMP-9 mRNA expression, MUC5B protein expression, and MMP-9 protein activity after the treatment with PMA, MMP-9 or doxycycline were determined by reverse transcriptase-polymerase chain reaction, enzyme immunoassay, gelatin zymography, and Western blot analysis. RESULTS: PMA increased MMP-9 and MUC5B expression. MMP-9 increased MUC5B expression. Doxycycline inhibited PMA-induced MUC5B expression, and PMA-induced MMP-9 mRNA expression and protein activity. Doxycycline inhibited phosphorylation of p38 induced by PMA and MMP-9. CONCLUSION: The results of this study suggest that doxycycline inhibited PMA-induced MUC5B mRNA expression and protein production through the MMP-9 and p38 pathways in human NCI-H292 airway epithelial cells.
