Involvement of Prostaglandin-Producing Pathway in the Cytotoxic Action of TUmor Necrosis Factor.

Hayakawa, Makio; Oku, Naoto; Takagi, Tatsuya; Hori, Takamitsu; Shibamoto, Sayumi; Yamanaka, Yoichi; Takeuchi, Kenji; Tsujimoto, Masafumi; Ito, F.

doi:10.1247/csf.16.333

Cited by 35 publications

(54 citation statements)

References 30 publications

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“…Phospholipase A 2 speci®cally cleaves AA from the sn2 position of membrane phospholipid, which is thereby released from the cells (Clark et al, 1991;Durstin et al, 1994;Hoeck et al, 1993). The TNF-induced lysis of susceptible cells is accompanied by the release of arachidonic acid (AA) into the culture media (Hayakawa et al, 1993). We showed that TNFinduced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A 2 was activated.…”

Section: Discussionmentioning

confidence: 93%

“…We showed that TNFinduced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A 2 was activated. Although it has been suggested that cPLA 2 is responsible for this e ect (Hayakawa et al, 1993;Voelkel-Johnson et al, 1996), the involvement of other forms of PLA 2 cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…The TNF-induced lysis of susceptible cells is accompanied by the release of arachidonic acid (AA) into the culture media (Hayakawa et al, 1993). The release of AA also accompanies the lysis of cells rendered sensitive to TNF by inhibitors of transcription or translation and some viral proteins (Bergovist et al, 1997;Krajcsi et al, 1996;Thorne et al, 1996;VoelkelJohnson et al, 1996).…”

Section: Sensitization Of Pbe6 Cells To Tnf-induced Apoptosis Is Accomentioning

confidence: 99%

“…The release of AA also accompanies the lysis of cells rendered sensitive to TNF by inhibitors of transcription or translation and some viral proteins (Bergovist et al, 1997;Krajcsi et al, 1996;Thorne et al, 1996;VoelkelJohnson et al, 1996). Previous work has demonstrated that activation of the 85 kDa cytosolic phospholipase A 2 (cPLA 2 ) is required for TNF cytolysis (Hayakawa et al, 1993;Hoeck et al, 1993;Voelkel-Johnson et al, 1996). These studies have also revealed that the activity of cPLA 2 is necessary for cell death.…”

Section: Sensitization Of Pbe6 Cells To Tnf-induced Apoptosis Is Accomentioning

confidence: 99%

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The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

et al. 1999

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Sensitization Of Pbe6 Cells To Tnf-induced Apoptosis Is Accomentioning

confidence: 99%

Section: Sensitization Of Pbe6 Cells To Tnf-induced Apoptosis Is Accomentioning

confidence: 99%

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The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

et al. 1999

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“…In L929 cells, TNF␣ treatment is known to produce potent cytotoxic effects (14). TNF␣-resistant L929 cells have also been generated via clonal selection from resistant populations of L929 mouse fibroblasts grown in the presence of TNF␣ (14,15). One of these cell lines, C12, differed from the original L929 cells by the absence of cPLA 2 and by the lack of inducibility of AA in response to TNF␣.…”

mentioning

confidence: 99%

Phospholipase A2 Is Necessary for Tumor Necrosis Factor α-induced Ceramide Generation in L929 Cells

Jayadev¹,

Hayter²,

Andrieu³

et al. 1997

Journal of Biological Chemistry

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151

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The role of cytosolic phospholipase A 2 (cPLA 2 ) in the regulation of ceramide formation was examined in a cell line (L929) responsive to the cytotoxic action of tumor necrosis factor ␣ (TNF␣). In L929 cells, the addition of TNF␣ resulted in the release of arachidonate, which was followed by a prolonged accumulation of ceramide occurring over 5-12 h and reaching 250% over base line. The formation of ceramide was accompanied by the hydrolysis of sphingomyelin and the activation of three distinct sphingomyelinases (neutral Mg 2؉ -dependent, neutral Mg 2؉ -independent, and acidic enzymes). The variant cell line C12, which lacks cPLA 2 , is resistant to the cytotoxic action of TNF␣. TNF␣ was able to activate nuclear factor B in both the wild-type L929 cells and the C12 cells. However, TNF␣ was unable to cause the release of arachidonate or the accumulation of ceramide in C12 cells. C 6 -ceramide overcame the resistance to TNF␣ and caused cell death in C12 cells to a level similar to that in L929 cells. The introduction of the cPLA 2 gene into C12 cells resulted in partial restoration of TNF␣-induced arachidonate release, ceramide accumulation, and cytotoxicity. This study suggests that cPLA 2 is a necessary component in the pathways leading to ceramide accumulation and cell death.The sphingomyelin (SM) 1 cycle, first described by Okazaki et al.(1), has gained recognition over the past few years as a key mechanism for regulating anti-mitogenic signals. Activation of this cycle through the regulation of a signal-induced sphingomyelinase (SMase) results in generation of the lipid second messenger ceramide. Ceramide then modulates a number of biological fates, including growth inhibition (1-3), differentiation (2), apoptosis (4 -6), and cell cycle arrest (7). Although recent studies have begun to catalogue inducers such as TNF␣, interleukin-1␤, nerve growth factor, and Fas that are capable of signaling through the SM cycle (see Refs. 5, 6, and 8 for reviews), the mechanisms by which these inducers stimulate SMase activity remain poorly understood.TNF␣, through interaction with either a 55-or 75-kDa TNF receptor (9, 10), impacts upon a myriad of intracellular signaling cascades, including protein phosphorylation cascades, transcription factors, and lipid messengers (11). Two classes of lipid mediators have been implicated in TNF␣ signaling, glycerophospholipid metabolites and sphingolipid metabolites (11,12), and recent evidence suggests that these two classes of lipids may interact (13). In HL-60 cells, a linear correlation was established among TNF␣ stimulation, AA generation, and SM cycle activation: TNF␣-stimulated AA liberation preceded ceramide generation, and AA reproduced the effects of TNF␣ on the SM cycle (13). Although these studies suggested that AA and/or its metabolites may be involved in activation of SMase, the physiologic role of the PLA 2 /AA pathway in regulating SMase activity has not been determined.In this study, we examined the role of PLA 2 in SMase activation in the L929 murine fibroblast cell l...

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Cytokine networks in solid human tumors: regulation of angiogenesis

Leek

Harris

Lewis

1994

Journal of Leukocyte Biology

193

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The isolation, purification, and molecular cloning of an increasing number of cytokines and their receptors have allowed major advances in our understanding of the relevance of these proteins to the pathobiology and treatment of such human diseases as neoplasia. Cytokines produced by the multiple cell types present within the microenvironment of solid tumors from a complex, dynamic network, in which they have overlapping properties, induce other cytokines and alter the expression of soluble and cell surface-bound cytokine receptors. A broad number of such intratumoral cytokines have multiple effects on tumor progression. These include direct and indirect effects both on tumor cell growth and metastatic behaviors and on such cells in the stromal compartment as fibroblasts, infiltrating immune cells, and endothelial cells in the microvasculature. Here, we review the sites of production and multifaceted role of several key cytokines in the stimulation of a new blood supply within growing neoplasms. The clinical implications and new therapeutic targets suggested by this rapidly emerging picture of the cellular and molecular mechanisms subserving tumor angiogenesis are also discussed.

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Involvement of Prostaglandin-Producing Pathway in the Cytotoxic Action of TUmor Necrosis Factor.

Cited by 35 publications

References 30 publications

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

Phospholipase A2 Is Necessary for Tumor Necrosis Factor α-induced Ceramide Generation in L929 Cells

Cytokine networks in solid human tumors: regulation of angiogenesis

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