Potentiation of Tumor Necrosis Factor α-induced Secreted Phospholipase A2 (sPLA2)-IIA Expression in Mesangial Cells by an Autocrine Loop Involving sPLA2 and Peroxisome Proliferator-activated Receptor α Activation

Beck, Stefanie; Lambeau, Gérard; Scholz-Pedretti, Kristen; Gelb, Michael H.; Janssen, Marcel J.W.; Edwards, Suzanne H.; Wilton, David C.; Pfeilschifter, Josef; Kaszkin, Marietta

doi:10.1074/jbc.m211763200

Cited by 86 publications

(80 citation statements)

References 67 publications

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“…Similar evidence was detected in culture media from human fibroblasts and chondrocytes (data not shown). High levels of sPLA 2 subtype, the so-called pancreatic-type sPLA 2 IB, are also found in the nondigestive tissues, including during acute pancreatitis (40,41), suggesting that group IB PLA 2 may also contribute to the pathophysiological effects in such conditions. In rat mesangial cells, exogenously added group IB PLA 2 can stimulate prostaglandin synthesis (42,43).…”

Section: Discussionmentioning

confidence: 99%

Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Choi

Lim

Kim

et al. 2004

Journal of Biological Chemistry

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Secretory phospholipase A 2 (sPLA 2 ), abundantly expressed in various cells including fibroblasts, is able to promote proliferation and migration. Degradation of collagenous extracellular matrix by matrix metalloproteinase (MMP) plays a role in the pathogenesis of various destructive disorders, such as rheumatoid arthritis, tumor invasion, and metastasis. Here we show that group IB PLA 2 increased pro-MMP-2 activation in NIH3T3 fibroblasts. MMP-2 activity was stimulated by group IB PLA 2 in a dose-and time-dependent manner. Consistent with MMP-2 activation, sPLA 2 decreased expression of type IV collagen. These effects are due to the reduction of tissue inhibitor of metalloproteinase-2 (TIMP-2) and the activation of the membrane type1-MMP (MT1-MMP). The decrease of TIMP-2 levels in conditioned media and the increase of MT1-MMP levels in plasma membrane were observed. In addition, treatment of cells with decanoyl Arg-Val-Lys-Arg-chloromethyl ketone, an inhibitor of pro-MT1-MMP, suppressed sPLA 2 -mediated MMP-2 activation, whereas treatment with bafilomycin A1, an inhibitor of H ؉ -ATPase, sustained MMP-2 activation by sPLA 2 . The involvement of phosphatidylinositol 3-kinase (PI3K) and Akt in the regulation of MMP-2 activity was further suggested by the findings that PI3K and Akt were phosphorylated by sPLA 2 . Expression of p85␣ and Akt mutants, or pretreatment of cells with LY294002, a PI3K inhibitor, attenuated sPLA 2 -induced MMP-2 activation and migration. Taken together, these results suggest that sPLA 2 increases the pro-MMP-2 activation and migration of fibroblasts via the PI3K and Akt-dependent pathway. Because MMP-2 is an important factor directly involved in the control of cell migration and the turnover of extracellular matrix, our study may provide a mechanism for sPLA 2 -promoted fibroblasts migration.

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Section: Discussionmentioning

confidence: 99%

Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Choi

Lim

Kim

et al. 2004

Journal of Biological Chemistry

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“…45 In this study, the contribution of exogenous secreted PLA 2 in the upregulation of PLA 2 IIA was calculated to be approximately 50%, whereas the remaining 50% was attributable to the cytokine stimulatory action. 45 Therefore, the secreted PLA 2 IIA released from HepG2 cells after proinflammatory cytokine stimulation may self-amplify the long-term total expression level of PLA 2 IIA. These phenomena may explain the discrepancies among 40% suppression on promoter activity, 40% suppression in mRNA expression level, and 96% suppression in protein expression level by UDCA in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…45 Beck et al 45 reported that PLA 2 IIA released from mesangial cells by TNF-␣ stimulates its own expression via an autocrine loop involving cytosolic PLA 2 and peroxisome proliferators-activated receptor ␣. 45 In this study, the contribution of exogenous secreted PLA 2 in the upregulation of PLA 2 IIA was calculated to be approximately 50%, whereas the remaining 50% was attributable to the cytokine stimulatory action. 45 Therefore, the secreted PLA 2 IIA released from HepG2 cells after proinflammatory cytokine stimulation may self-amplify the long-term total expression level of PLA 2 IIA.…”

Section: Discussionmentioning

confidence: 99%

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

et al. 2005

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“…This finding corroborates recent results obtained in mesangial cells using heparinase-1. 19 Unlike this pharmacological compound, the use of sPLA2-IIA mutants eliminates the possibility of a release of truncated heparin sulfate chains from the cell surface. Proteoglycans function as a type of receptor system for fibroblast growth factor and for members of the opiate receptor family.…”

Section: Amandine Et Almentioning

confidence: 99%

Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells

Jaulmes

Janvier

Andreani

et al. 2005

ATVB

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Objective-The inflammation that occurs during the development of atherosclerosis is characterized by a massive release of sPLA2-IIA (group IIA secretory phospholipase A2) from vascular smooth muscle cells (VSMCs). We have investigated the autocrine function of sPLA2-IIA in rat aortic and human VSMCs. Methods and Results-We found that the transcription of the endogenous sPLA2-IIA gene increased by adding a cell supernatant containing human sPLA2-IIA proteins. We show that this effect was independent of the sPLA2 activity using sPLA2-IIA proteins lacking enzyme activity. Transient transfections with various sPLA2-IIA rat promoterluciferase constructs demonstrated that the C/EBP, NK-B, and Ets transcription factors are involved in the increase in sPLA2-IIA gene transcription. We also found the M-type sPLA2 receptor mRNA in VSMCs, and we showed that the sPLA2-luciferase reporter gene was induced by the specific agonist of the sPLA2 receptor, aminophenylmannopyranoside (APMP), and that this induction was mediated by the same transcription factor-binding sites. Finally, we used a sPLA2-IIA mutant unable to bind heparan-sulfate proteoglycans to show that the binding of wild-type sPLA2-IIA to proteoglycans is essential for the induction of an autocrine loop. Key Words: atherosclerosis Ⅲ autocrine/paracrine effects Ⅲ type IIA sPLA2 Ⅲ vascular smooth muscle cells P hospholipase A2 (PLA2) enzymes (EC 3.1.1.4) hydrolyze ester bonds at the sn-2 position of glyceroacylphospholipids to produce lysophospholipids and nonesterified fatty acids such as arachidonic acid (C20:4 n-6). The latter is further metabolized, contributing to the proinflammatory actions and later resolution. 1 PLA2 enzymes are present in most tissues and 4 groups are distinguished by subcellular location, molecular weight, and calcium dependence. One of these groups is secretory PLA2s (sPLA2s). The sPLA2s are extracellular low-molecular-mass (13 to 18 kDa) enzymes that have 6 to 8 disulfide bridges and require millimolar concentrations of Ca 2ϩ . 2 The isoform sPLA2-IIA is the most abundant sPLA2 in vascular smooth muscle cells (VSMCs). 3 Its synthesis is stimulated by inflammatory cytokines such as interleukin 1␤ (IL-1␤), IL-6, and tumor necrosis factor-1␣. 4 The plasma of patients with various inflammatory diseases, particularly atherosclerosis, contains high concentrations of sPLA2-IIA. 5,6 Transgenic mice that overproduce human sPLA2-IIA have confirmed its involvement in atherosclerosis. 7 sPLA2-IIA also functions as a messenger, and this latter function can be independent of its enzymatic activity. For example, sPLA2-IIA triggers a signaling cascade in monocytic cells that has features similar to those found in other cell types and seems to be unrelated to its catalytic activity. 8,9 The recent identification of membrane proteins binding sPLA2 has highlighted the biological effects of these enzymes. Several studies have shown that sPLA2-IB and sPLA2-IIA act via specific receptors characterized in several species (M-type receptors) to play roles that are...

show abstract

Potentiation of Tumor Necrosis Factor α-induced Secreted Phospholipase A2 (sPLA2)-IIA Expression in Mesangial Cells by an Autocrine Loop Involving sPLA2 and Peroxisome Proliferator-activated Receptor α Activation

Cited by 86 publications

References 67 publications

Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells

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