Exp Mol Med.  2009 Apr;41(4):259-268. 10.3858/emm.2009.41.4.029.

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

• Lee YS
• Lan Tran H
• Van Ta Q

• KMID: 1088601
• DOI: http://doi.org/10.3858/emm.2009.41.4.029

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.

Keyword

anthra(1,9-cd)pyrazol-6(2H)-one; autocrine communication; JNK mitogen-activated protein kinases; macrophages; matrix metalloproteinase 9; serum

MeSH Terms

Animals
Anthracenes/metabolism
Cell Line
Culture Media, Conditioned/*chemistry
Enzyme Activation
Enzyme Induction
Enzyme Inhibitors/metabolism
Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
*Gene Expression Regulation, Enzymologic
MAP Kinase Signaling System/physiology
Macrophages/cytology/*metabolism
Matrix Metalloproteinase 9/genetics/*metabolism
Mice
Mitogen-Activated Protein Kinase 8/genetics/*metabolism
NF-kappa B/genetics/metabolism
Proto-Oncogene Proteins c-akt/genetics/metabolism
Tumor Necrosis Factor-alpha/metabolism
p38 Mitogen-Activated Protein Kinases/genetics/metabolism