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Pam3CSK4 Induces MMP-9 Expression in Human Monocytic THP-1 Cells.
- Source :
- Cellular Physiology & Biochemistry (Karger AG); Jun2017, Vol. 41 Issue 5, p1993-2003, 11p
- Publication Year :
- 2017
-
Abstract
- Background: Matrix metalloproteinase (MMP)-9 is known to degrade the extracellular matrix and increased MMP-9 levels are related with the pathogenesis of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic triacylated lipopeptide (LP) which is a potent activator of immune cells and induces cytokine production. However, it is unclear whether Pam3CSK4 is able to induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9 production by Pam3CSK4-treated THP-1 cells and also investigated the signal transduction pathway(s) involved. Methods: MMP-9 expression was determined by real-time qPCR and ELISA. MMP-9 activity was assessed by zymography. THP-1 cells, THP1- XBlue™ cells, THP1-XBlue™-defMyD cells, anti-TLR2 mAb and selective pharmacological inhibitors were used to study signaling pathways involved. Phosphorylated and total proteins were detected by western blotting. Results: Pam3CSK4 induced MMP-9 expression (P<0.05) at both mRNA and protein levels in human monocytic THP-1 cells. Increased NF-κB/AP-1 activity was detected in Pam3CSK4-treated THP-1 cells and MMP-9 production in these cells was significantly suppressed by pre-treatment with anti-TLR2 neutralizing antibody or by inhibition of clathrin-dependent endocytosis. Also, MyD88-/- THP-1 cells did not express MMP-9 following treatment with Pam3CSK4. Inhibition of JNK, MEK/ERK, p38 MAPK and NF-κB significantly suppressed MMP-9 gene expression (P<0.05). Conclusion: Pam3CSK4 induces MMP-9 production in THP-1 cells through the TLR-2/MyD88-dependent mechanism involving MEK/ERK, JNK, p38 MAPK and NF-κB/AP-1 activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10158987
- Volume :
- 41
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cellular Physiology & Biochemistry (Karger AG)
- Publication Type :
- Academic Journal
- Accession number :
- 123770540
- Full Text :
- https://doi.org/10.1159/000475298