Regulation of expression of matrix metalloproteinase-9 by JNK in Raw 264.7 cells: presence of inhibitory factor(s) suppressing MMP-9 induction in serum and conditioned media
Experimental & Molecular Medicine
; : 259-268, 2009.
Article
in En
| WPRIM
| ID: wpr-49341
Responsible library:
WPRO
ABSTRACT
Matrix metalloproteinase-9 (MMP-9) secreted from macrophages plays an important role in tissue destruction and inflammation through degradation of matrix proteins and proteolytic activation of cytokines/chemokines. Whereas the MEK-ERK and PI3K-Akt pathways up-regulate MMP-9 expression, regulation of MMP-9 by JNK remains controversial. Presently, we aimed to determine the role of JNK in MMP-9 regulation in Raw 264.7 cells. Inhibition of JNK by the JNK inhibitor SP600125 induced MMP-9 in the absence of serum and suppressed the expression of TNF-alpha, IL-6 and cyclooxygenase-2 in LPS-treated Raw 264.7 cells. In a knockdown experiment with small interfering RNA, suppression of JNK1 induced MMP-9 expression. Interestingly, mouse serum suppressed SP600125-mediated MMP-9 induction, similar to IFN-gamma. However, the inhibitory activity of mouse serum was not affected by pyridone 6, which inhibits Janus kinase downstream to IFN-gamma. In addition to mouse serum, conditioned media of Raw 264.7 cells contained the inhibitory factor(s) larger than 10 kDa, which suppressed SP600125- or LPS-induced MMP-9 expression. Taken together, these data suggest that JNK1 suppresses MMP-9 expression in the absence of serum. In addition, the inhibitory factor(s) present in serum or secreted from macrophages may negatively control MMP-9 expression.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Gene Expression Regulation, Enzymologic
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Cell Line
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Enzyme Induction
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NF-kappa B
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Tumor Necrosis Factor-alpha
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Culture Media, Conditioned
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Matrix Metalloproteinase 9
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MAP Kinase Signaling System
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinase 8
Limits:
Animals
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2009
Type:
Article