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Clarithromycin inhibits TNF-α-induced MUC5AC mucin gene expression via the MKP-1-p38MAPK-dependent pathway
- Source :
- International Immunopharmacology. 49:60-66
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases. It was recently reported that MKP-1 appears to mediate the effects of several anti-inflammatory drugs, including glucocorticoids, but the role of MKP-1 on mucin gene expression in the presence of macrolides in the human airway remains unknown. Here, we demonstrate that the MKP-1 protein is induced by clarithromycin and that clarithromycin suppresses TNF-α-induced MUC5AC mucin gene expression in a p38 MAPK-dependent manner in human airway epithelial (NCI-H292) cells. Our study thus provides new insights into the role of MKP-1 in mediating the effects of macrolides and may help in the development of new therapeutic strategies against mucin overproduction.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Chronic bronchitis
p38 mitogen-activated protein kinases
Immunology
Bronchi
Mucin 5AC
Biology
p38 Mitogen-Activated Protein Kinases
Cell Line
03 medical and health sciences
0302 clinical medicine
Clarithromycin
Dual-specificity phosphatase
Humans
Immunology and Allergy
Sinusitis
Pharmacology
Regulation of gene expression
Tumor Necrosis Factor-alpha
Kinase
Mucin
Dual Specificity Phosphatase 1
Epithelial Cells
Anti-Bacterial Agents
Bronchitis, Chronic
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
Chronic Disease
Cancer research
biology.protein
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....f7a59359b949a67c9f47b2215dce3a64