Matrix Metalloproteinase-9 and Autoimmune Diseases

Ram, Maya; Sherer, Yaniv; Shoenfeld, Yehuda

doi:10.1007/s10875-006-9022-6

Cited by 246 publications

(205 citation statements)

References 31 publications

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“…The transcription of MMP-9 gene is under the control of a 2.2-kb upstream regulatory sequence harboring binding sites for AP-1, NF-B, SP-1, and PEA3/Ets, which are conserved in both human and mouse (9,39,40). Accumulating evidence suggests that the activation of NF-B is one of the most important signaling events required for the inducible expression of MMP-9 in response to different stimuli (14).…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

107

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Destruction of skeletal muscle extracellular matrix is an important pathological consequence of many diseases involving muscle wasting. However, the underlying mechanisms leading to extracellular matrix breakdown in skeletal muscle tissues remain unknown. Using a microarray approach, we investigated the effect of tumor necrosis factor-related weak inducer of apoptosis (TWEAK), a recently identified muscle-wasting cytokine, on the expression of extracellular proteases in skeletal muscle. Among several other matrix metalloproteinases (MMPs), we found that the expression of MMP-9, a type IV collagenase, was drastically increased in myotubes in response to TWEAK. The level of MMP-9 was also higher in myofibers of TWEAK transgenic mice. TWEAK increased the activation of both classical and alternative nuclear factor-B (NF-B) signaling pathways. Inhibition of NF-B activity blocked the TWEAK-induced production of MMP-9 in myotubes. TWEAK also increased the activation of AP-1, and its inhibition attenuated the TWEAK-induced MMP-9 production. Overexpression of a kinase-dead mutant of NF-B-inducing kinase or IB kinase-␤ but not IB kinase-␣ significantly inhibited the TWEAK-induced activation of MMP-9 promoter. The activation of MMP-9 also involved upstream recruitment of TRAF2 and cIAP2 proteins. TWEAK increased the activity of ERK1/2, JNK1, and p38 MAPK. However, the inhibition of only p38 MAPK blocked the TWEAK-induced expression of MMP-9 in myotubes. Furthermore the loss of body and skeletal muscle weights, inflammation, fiber necrosis, and degradation of basement membrane around muscle fibers were significantly attenuated in Mmp9 knock-out mice on chronic administration of TWEAK protein.The study unveils a novel mechanism of skeletal muscle tissue destruction in pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

107

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“…Shown in Supporting information, Table S2, are transcripts changed significantly with either sitagliptin or placebo treatment (P < 0·001) that had a fold change > 1·2. One of the transcripts with the highest significance and fold change was matrix metallopeptidase 9, a protein important for leucocyte trafficking that is up-regulated in many autoimmune diseases [26]. Another gene changed significantly in the sitagliptin group was small ubiquitin-related modifier (SUMO-1), that can modify other proteins via sumoylation.…”

Section: Cd26mentioning

confidence: 99%

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Price

Linder

et al. 2013

Clinical and Experimental Immunology

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SummarySitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

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“…The matrix metalloproteinase (MMP) family consists of a group of closely associated enzymes involved in the cleavage of structural components of the extracellular matrix (ECM); these enzymes are considered to be essential factors involved in tumor invasion and metastasis (11,12). In gastric cancer, MMP-9 and MMP-2 were reported to be overexpressed and associated with tumor aggressiveness (11,12).…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase-2 expression

2015

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Abstract. Cyclooxygenase-2 (COX-2) has a critical role in the invasiveness and metastasis of gastric cancer. In addition, paclitaxel (PTX) and harmine (HM) were reported to be potential therapeutic drug candidates for cancer therapy; however, the synergistic antitumor effect of PTX and HM combined treatment on the human gastric cancer cells remains to be elucidated. The aim of the present study was to evaluate the effects of PTX and/or HM on the cell migration and invasion in two human gastric cancer cell lines, SGC-7901 and MKN-45. MTT assay was used to detect the growth inhibition induced by PTX and HM . The Transwell assay was employed to assess the effects of PTX and HM on the cell migration and invasion. The expression levels of COX-2 and matrix metalloproteinase-9 (MMP-9) were analyzed by western blot analysis. The results demonstrated that PTX and HM inhibited cell proliferation in a dose-dependent manner. Individually PTX and HM were able to inhibit the migration and invasion of two human gastric cancer cells; however, the combination of PTX and HM exerted synergistic effects on migration and invasion inhibition, with downregulation of COX-2 and matrix metalloproteinase (MMP)-9. In conclusion, the results of the present study indicated that combination chemotherapy using PTX with HM exerted an antitumor effect, which may be implicated for the treatment of gastric cancer. Of note, the combination of the two drugs inhibited migration and invasion more effectively compared with each drug alone, the mechanism of which proceeded via the downregulation of COX-2 expression.

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Matrix Metalloproteinase-9 and Autoimmune Diseases

Cited by 246 publications

References 31 publications

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase-2 expression

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