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.
10.3858/emm.2009.41.4.029
- Author:
Yun Song LEE
1
;
Huong Thi LAN TRAN
;
Quang VAN TA
Author Information
1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Korea. yslee@skku.edu
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
anthra(1,9-cd)pyrazol-6(2H)-one;
autocrine communication;
JNK mitogen-activated protein kinases;
macrophages;
matrix metalloproteinase 9;
serum
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(4):259-268
- CountryRepublic of Korea
- Language:English
-
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.
