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MMP-9 Production (mmp-9 + production)
Selected AbstractsRole of EG-VEGF in human placentation: Physiological and pathological implicationsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Pascale Hoffmann Abstract Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE. [source] Activated ,2 macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-,B activation in macrophage-derived cell linesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Leandro C. Cáceres Abstract Macrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-,B signaling pathways. Previously, we demonstrated that activated ,2 -macroglulin (,2M*) through the interaction with its receptor low-density lipoprotein receptor-related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK-ERK1/2. In the present work, we examined whether ,2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that ,2M* promoted MMP-9 expression and protein secretion by LRP1 in both macrophage-derived cell lines, which was mediated by the activation of MAPK-ERK1/2 and NF-,B. Both intracellular signaling pathways activated by ,2M* were effectively blocked by calphostin-C, suggesting involvement of PKC. In addition, we demonstrate that ,2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the ,2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1, and NF-,B, it was shown that the ,2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the ,2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression. J. Cell. Biochem. 111: 607,617, 2010. © 2010 Wiley-Liss, Inc. [source] Interleukin-1, induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-,B signaling pathways in human tracheal smooth muscle cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Kao-Chih Liang Matrix metalloproteinases (MMPs) are responsible for degradation of extracellular matrix and play important roles in cell migration, proliferation, and tissue remodeling related to airway inflammation. Interleukin-1, (IL-1,) has been shown to induce MMP-9 production in many cell types and contribute to airway inflammatory responses. However, the mechanisms underlying MMP-9 expression induced by IL-1, in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here, we investigated the roles of p42/p44 MAPK, p38 MAPK, JNK, and NF-,B pathways for IL-1,-induced MMP-9 production in HTSMCs. IL-1, induced production of MMP-9 protein and mRNA in a time- and concentration-dependent manner determined by zymographic, Western blotting, and RT-PCR analyses, which was attenuated by inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), JNK (SP600125), and NF-,B (helenalin), and transfection with dominant negative mutants of MEK1/2, p38 and JNK, respectively. IL-1,-stimulated phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK was attenuated by pretreatment with U0126, SB202190, SP600125, or transfection with these dominant negative mutants of MEK, ERK, p38 and JNK, respectively. Furthermore, IL-1,-stimulated translocation of NF-,B into the nucleus and degradation of I,B-, was blocked by helenalin. Finally, the reporter gene assay revealed that MAPKs and NF-,B are required for IL-1,-induced MMP-9 luciferase activity in HTSMCs. MMP-9 promoter activity was enhanced by IL-1, in HTSMCs transfected with MMP-9-Luc, which was inhibited by helenalin, U0126, SB202190, and SP600125. Taken together, the transcription factor NF-,B, p42/p44 MAPK, p38 MAPK, and JNK that are involved in MMP-9 expression in HTSMCs exposed to IL-1, have now been identified. J. Cell. Physiol. 211: 759,770, 2007. © 2007 Wiley-Liss, Inc. [source] C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metalloproteinasesTHE JOURNAL OF PATHOLOGY, Issue 5 2004Toshiyuki Okuma Abstract Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2,/,) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 ,/, mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2,/, and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2,/, mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2,/, mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2,/, mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2,/, mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2,/, mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||