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 TM cells, THP1-XBlueTM-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.
Original language | English |
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Pages (from-to) | 1993-2003 |
Number of pages | 11 |
Journal | Cellular Physiology and Biochemistry |
Volume | 41 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Jun 2017 |
Keywords
- MMP-9
- Pam3CSK4
- THP-1 cells
- TLR2