Products of the lipoxygenase pathway in human natural killer cell cytotoxicity

Rossi, Paolo; Lindgren, Jan; Kullman, Charlotte; Jondal, Mikael

doi:10.1016/0008-8749(85)90383-1

Cited by 21 publications

(6 citation statements)

References 34 publications

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“…Interestingly, although NKG2D engagement induces 5-LO and COX activation, only 5-LO is involved in NKG2D-mediated cytolysis (unpublished data). These observations are in agreement with reports suggesting that leukotrienes, but not prostaglandins, play a role in lymphokine-activated killer activity (51, 52) and NK-mediated cytolysis (69, 70).…”

Section: Discussionsupporting

confidence: 93%

Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

Tang

Chen

Ciszewski

et al. 2009

Journal of Experimental Medicine

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IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets.

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Section: Discussionsupporting

confidence: 93%

Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

Tang

Chen

Ciszewski

et al. 2009

Journal of Experimental Medicine

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“…The present results demonstrate that sub-nanomolar concentrations of LTB 4 induced enhancement of NT-4 mRNA expression in granulocytes. The response was observed at a concentration normally reported to elicit optimal physiological effects in various systems [44][45][46]. It is interesting to note that the LTB 4 -induced effect was specific for NT-4, since the expression of NGF and BDNF mRNAs was unchanged.…”

Section: Discussionmentioning

confidence: 82%

“…The response was observed at a concentration normally reported to elicit optimal physiological effects in various systems [44][45][46]. It is interesting to note that the LTB 4 -induced effect was specific for NT-4, since the expression of NGF and BDNF mRNAs was unchanged.…”

Section: Discussionmentioning

confidence: 96%

Expression of mRNA encoding neurotrophins and neurotrophin receptors in human granulocytes and bone marrow cells—enhanced neurotrophin-4 expression induced by LTB4

Laurenzi

Beccari

Stenke

et al. 1998

Journal of Leukocyte Biology

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The expression of neurotrophin and neurotrophin receptor mRNAs in human granulocytes and bone marrow cells was examined using ribonuclease protection assay and reverse transcription-polymerase chain reaction. The granulocytes expressed mRNA coding for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3). Moreover, the inflammatory mediator leukotriene B 4 (LTB 4 ) up-regulated the expression of NT-4 mRNA in granulocytes, but did not affect the expression of other neurotrophin mRNAs. Granulocytes generally lacked expression of mRNA coding for neurotrophin receptors. In contrast, human bone marrow cells consistently expressed mRNA for trkB (the BDNF and NT-4 receptor) and displayed variable expression of mRNA coding for trkA (the tyrosine kinase NGF receptor) and LNGFR (the low-affinity NGF receptor), whereas mRNA for trkC (the NT-3 receptor) was not expressed. Contrary to granulocytes, normal bone marrow cells generally expressed only low levels of mRNA encoding BDNF and NT-4. Expression of mRNA encoding NGF and NT-3 was not detected. However, significantly increased expression of BDNF mRNA was observed when bone marrow cells from patients with chronic myeloproliferative disorders (MPD) were analyzed. The results suggest that neurotrophins may act as granulocyte-derived effector molecules and that human bone marrow cells may be targets for these compounds, in particular BDNF and NT-4. J. Leukoc. Biol. 64: 228-234; 1998.

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“…The NK protection is activated by leucotriene LTB4 formed by lipoxygenase, and inhibited by the fever prostaglandin PGE2 formed by cycloxygenase [86]. Hence, inhibitors of PGE2 and cycloxygenase trigger the NK protection; this is an effect of non-steroid anti-inflammatory drugs (NSAIDS) aspirin, ibuprofen, or of some histone acetylase (HAT) inhibitors (curcumin, anacardic acid garcinol etc...).…”

Section: Cancer Prevention Immune Destruction Of Tumor Cellsmentioning

confidence: 99%

The metabolic advantage of tumor cells

2011

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1- Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors. Other oncogenes alter the PP2A phosphatase brake over these kinases.2- Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas.Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases.3- Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase. In addition, demethylated PP2A would no longer dephosphorylate these enzymes. A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination. This pyruvate forms lactate (Warburg effect) and NAD+ for glycolysis. Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available. ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis. Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis.4- The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase)5- IGFBP stops binding the IGF - IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability.6- An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...

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Products of the lipoxygenase pathway in human natural killer cell cytotoxicity

Cited by 21 publications

References 34 publications

Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

Expression of mRNA encoding neurotrophins and neurotrophin receptors in human granulocytes and bone marrow cells—enhanced neurotrophin-4 expression induced by LTB4

The metabolic advantage of tumor cells

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