Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated‘qc fatty acids

Robinson, B S; Hii, Charles S.; Poulos, A.; Fèrrante, Antonio

doi:10.1046/j.1365-2567.1997.d01-2227.x

Cited by 77 publications

(54 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neutrophils contain PKC ␣, ␤I, ␤II, ␦, and (28). Although polyunsaturated fatty acids have been reported to stimulate Ca 2ϩ mobilization (29), activate the neutral sphingomyelinase (30), and amplify H ϩ ion channel conductance (31) in intact neutrophils and to stimulate GTP␥S loading of the heterotrimeric G-proteins in neutrophil membrane fractions (32), the effect of fatty acids on PKC translocation in neutrophils has not been reported. In unstimulated neutrophils, a substantial amount of PKC ␤II was detected in a particulate fraction, and this was increased after incubation with 20:4 6 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The non-esterified 20:4 6 that is released has been found to be cell-associated as well as being released into the extracellular medium. Thus, many studies have assayed for the appearance of radiolabeled 20:4 6 in the extracellular medium as a measure of phospholipase A 2 activation (1,35,36). Although cell-associated 20:4 6 can directly serve as an endogenous second messenger and is a substrate for the lipoxygenases and cyclooxygenases, 20:4 6 that is released into the extracellular fluid has the potential to exert autocrine and paracrine effects.…”

Section: Resultsmentioning

confidence: 99%

“…After centrifugation (16,000 ϫ g, 5 min), the beads were washed once with buffer A, once with wash buffer (10 mM Pipes, pH 7, 100 mM NaCl, and the protease inhibitors, which were added to buffer A) and once with assay buffer (see p38 above). The assay was started by adding 35 l assay buffer containing 8 Ci of ␥ 32 P-ATP and bringing the temperature to 30°C. After 20 min, the assay was terminated by the addition of Laemmli buffer and boiling the samples for 5 min at 100°C.…”

Section: Preparation Of Cellular Extractsmentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of p38 Phosphorylation and Activity by Arachidonic Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human Neutrophils

Hii¹,

Huang²,

Bilney³

et al. 1998

Journal of Biological Chemistry

100

101

View full text Add to dashboard Cite

Although it is well appreciated that arachidonic acid, a second messenger molecule that is released by ligandstimulated phospholipase A 2 , stimulates a wide range of cell types, the mechanisms that mediate the actions of arachidonic acid are still poorly understood. We now report that arachidonic acid stimulated the appearance of dual-phosphorylated (active) p38 mitogen-activated protein kinase as detected by Western blotting in HeLa cells, HL60 cells, human neutrophils, and human umbilical vein endothelial cells but not Jurkat cells. An increase in p38 kinase activity caused by arachidonic acid was also observed. Further studies with neutrophils show that the stimulation of p38 dual phosphorylation by arachidonic acid was transient, peaking at 5 min, and was concentration-dependent. The effect of arachidonic acid was not affected by either nordihydroguaiaretic acid, an inhibitor of the 5-, 12-, and 15-lipoxygenases or by indomethacin, an inhibitor of cyclooxygenase. Arachidonic acid also stimulated the phosphorylation and/or activity of the extracellular signal-regulated protein kinase and of c-jun N-terminal kinase in a cell-typespecific manner. An examination of the mechanisms through which arachidonic acid stimulated the phosphorylation/activity of p38 and extracellular signal-regulated protein kinase in neutrophils revealed an involvement of protein kinase C. Thus, arachidonic acid stimulated the translocation of protein kinase C ␣, ␤I, and ␤II to a particulate fraction, and the effects of arachidonic acid on mitogen-activated protein kinase phosphorylation/activity were partially inhibited by GF109203X, an inhibitor of protein kinase C. This study is the first to demonstrate that a polyunsaturated fatty acid causes the dual phosphorylation and activation of p38.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Cellular Extractsmentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of p38 Phosphorylation and Activity by Arachidonic Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human Neutrophils

Hii¹,

Huang²,

Bilney³

et al. 1998

Journal of Biological Chemistry

100

101

View full text Add to dashboard Cite

show abstract

“…␤-oxa, ␤-thia, and ␥-thia PUFA and their methyl esters were synthesized, as described previously (5)(6)(7)(8). All fatty acid stocks (20 mM in chloroform or ethanol) were stored at Ϫ20°C.…”

Section: Fatty Acidsmentioning

confidence: 99%

The Immunomodulatory Effects of Novel β-Oxa, β-Thia, and γ-Thia Polyunsaturated Fatty Acids on Human T Lymphocyte Proliferation, Cytokine Production, and Activation of Protein Kinase C and MAPKs

Costabile

Hii

Melino

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

We have recently demonstrated that a novel n-3 long chain polyunsaturated fatty acid (PUFA) (β-oxa 21:3n-3) was a more potent and more selective anti-inflammatory agent than n-3 PUFA. To gain further insights into this technology, we synthesized other novel PUFA consisting of β-oxa, β-thia, and γ-thia compounds. All three types displayed anti-inflammatory activity. Each of the unsaturated β-oxa fatty acids showed similar inhibition of PHA-PMA-induced T cell proliferation with a parallel inhibition of TNF-β production. However, β-oxa 25:6n-3 and β-oxa 21:4n-3 displayed lower inhibitory action on IFN-γ production. Surprisingly, β-oxa 23:4n-6 and β-oxa 21:3n-6 had marginal effect on IL-2 production. Thus, structural variation can generate selectivity for different immunological parameters. The β-thia compounds 23:4n-6, 21:3n-6, and 21:3n-3 were highly effective in inhibiting all immunological responses. Of the two γ-thia PUFA tested, γ-thia 24:4n-6 was a strong inhibitor of all responses apart from IL-2, but γ-thia 22:3n-6 had very little inhibitory effect. Two of the most active compounds, β-thia 23:4n-6 and β-thia 21:3n-6, were studied in more detail and shown to have an IC50 of 1–2 μM under optimal conditions. Thus, these PUFA retain the immunosuppressive properties of the n-3 PUFAs, 20:5n-3 and 22:6n-3, but not the neutrophil-stimulating properties. Their action on T lymphocytes is independent of cyclooxygenase or lipoxygenase activity, and they act at a postreceptor-binding level by inhibiting the activation of protein kinase C and ERK1/ERK2 kinases.

show abstract

“…Fatty acid methyl esters were synthesized, as described previously (10). The 22:6n-3 (Sigma, St. Louis, MO) and all fatty acid stocks (20 mM in chloroform or ethanol) were stored at Ϫ20°C.…”

Section: Fatty Acidsmentioning

confidence: 99%

A Novel Long Chain Polyunsaturated Fatty Acid, β-Oxa 21:3n-3, Inhibits T Lymphocyte Proliferation, Cytokine Production, Delayed-Type Hypersensitivity, and Carrageenan-Induced Paw Reaction and Selectively Targets Intracellular Signals

Costabile

Hii

Robinson

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

A novel polyunsaturated fatty acid (PUFA), β-oxa 21:3n-3, containing an oxygen atom in the β position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the immune system. Although β-oxa 21:3n-3 was very poor compared with 22:6n-3 at stimulating oxygen radical production in neutrophils, it was more effective at inhibiting human T lymphocyte proliferation (IC50 of 1.9 vs 5.2 μM, respectively). β-Oxa 21:3n-3 also inhibited the production of TNF-β, IFN-γ, and IL-2 by purified human T lymphocytes stimulated with PHA plus PMA, anti-CD3 plus anti-CD28 mAbs, or PMA plus A23187. Metabolism of β-oxa 21:3n-3 via the cyclooxygenase and lipoxygenase pathways was not required for its inhibitory effects. Consistent with its ability to suppress T lymphocyte function, β-oxa 21:3n-3 significantly inhibited the delayed-type hypersensitivity response and carrageenan-induced paw edema in mice. In T lymphocytes, β-oxa 21:3n-3 inhibited the agonist-stimulated translocation of protein kinase C-βI and -ε, but not -α, -βII, or -θ to a particulate fraction, and also inhibited the activation of the extracellular signal-regulated protein kinase, but not c-Jun NH2-terminal kinase and p38. In contrast, 22:6n-3 had no effects on these protein kinase C isozymes. The increase in antiinflammatory activity and loss of unwanted bioaction through the generation of a novel synthetic 22:6n-3 analogue provides evidence for a novel strategy in the development of anti-inflammatory agents by chemically engineering PUFA.

show abstract

Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated‘qc fatty acids

Cited by 77 publications

References 39 publications

Stimulation of p38 Phosphorylation and Activity by Arachidonic Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human Neutrophils

Stimulation of p38 Phosphorylation and Activity by Arachidonic Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human Neutrophils

The Immunomodulatory Effects of Novel β-Oxa, β-Thia, and γ-Thia Polyunsaturated Fatty Acids on Human T Lymphocyte Proliferation, Cytokine Production, and Activation of Protein Kinase C and MAPKs

A Novel Long Chain Polyunsaturated Fatty Acid, β-Oxa 21:3n-3, Inhibits T Lymphocyte Proliferation, Cytokine Production, Delayed-Type Hypersensitivity, and Carrageenan-Induced Paw Reaction and Selectively Targets Intracellular Signals

Contact Info

Product

Resources

About