Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C

dc.contributor.authorTintinger, Gregory Ronald
dc.contributor.authorTheron, Annette J.
dc.contributor.authorSteel, Helen Carolyn
dc.contributor.authorCockeran, Riana
dc.contributor.authorPretorius, Lynette
dc.contributor.authorAnderson, Ronald
dc.contributor.emailannette.theron@up.ac.zaen
dc.date.accessioned2010-04-06T07:09:40Z
dc.date.available2010-04-06T07:09:40Z
dc.date.issued2009-10
dc.description.abstractBACKGROUND: The role of protein kinase C (PKC) in regulating the activity of phospholipase C (PLC) in neutrophils activated with the chemoattractant, platelet-activating factor (PAF, 20 and 200 nM), was probed in the current study using the selective PKC inhibitors, GF10903X (0.5 - 1 μM) and staurosporine (400 nM). METHODS: Alterations in cytosolic Ca2+, Ca2+ influx, inositol triphosphate (IP3), and leukotriene B4 production were measured using spectrofluorimetric, radiometric and competitive binding radioreceptor and immunoassay procedures, respectively. RESULTS: Activation of the cells with PAF was accompanied by an abrupt increase in cytosolic Ca2+ followed by a gradual decline towards basal levels. Pretreatment of neutrophils with the PKC inhibitors significantly increased IP3 production with associated enhanced Ca2+ release from storage vesicles, prolongation of the peak cytosolic Ca2+ transients, delayed clearance and exaggerated reuptake of the cation, and markedly increased synthesis of LTB4. The alterations in Ca2+ fluxes observed with the PKC inhibitors were significantly attenuated by U73122, a PLC inhibitor, as well as by cyclic AMP-mediated upregulation of the Ca2+-resequestering endomembrane ATPase.Taken together, these observations are compatible with a mechanism whereby PKC negatively modulates the activity of PLC, with consequent suppression of IP3 production and down-regulation of Ca2+ mediated pro-inflammatory responses of PAF-activated neutrophils. CONCLUSION: Although generally considered to initiate and/or amplify intracellular signalling cascades which activate and sustain the pro-inflammatory activities of neutrophils and other cell types, the findings of the current study have identified a potentially important physiological, anti-inflammatory function for PKC, at least in neutrophils.en
dc.identifier.citationTintinger, GR, Theron, AJ, Steel, HC, Cockeran, R, Pretorius, L & Anderson, R 2009, 'Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C', Journal of Inflammation, vol. 6, no. 29, pp. 1-9e. [http://www.journal-inflammation.com]en
dc.identifier.issn1476-9255
dc.identifier.other10.1186/1476-9255-6-29
dc.identifier.urihttp://hdl.handle.net/2263/13791
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rights© 2009 Tintinger et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectCalcium homeostasisen
dc.subjectChemoattractanten
dc.subject.lcshProtein kinase Cen
dc.subject.lcshCalcium -- Researchen
dc.subject.lcshNeutrophils -- Immunologyen
dc.subject.lcshPlatelet activating factoren
dc.subject.lcshPhospholipase Cen
dc.subject.lcshChemical inhibitorsen
dc.subject.lcshAnti-inflammatory agentsen
dc.titleProtein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase Cen
dc.typeArticleen

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