Clin Exp Otorhinolaryngol.  2011 Dec;4(4):177-183.

The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea. ydkim@med.yu.ac.kr
  • 2Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.
  • 3Center for Respiratory Disease, Yeungnam University Medical Center, Daegu, Korea.

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.

Keyword

Doxycycline; Inflammation; Phorbol myristate acetate; Matrix metalloproteinase-9; p38; Mucins; MUC5B; Epithelial cells; NCI-H292 cell

MeSH Terms

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
Doxycycline
Gelatin
Matrix Metalloproteinase 9
Mucins
Phorbols
Protein Kinase C
RNA, Messenger
Tetradecanoylphorbol Acetate
Thiram
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