Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor

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dc.contributor.authorSuram, Saritha
dc.contributor.authorBrown, Gordon D
dc.contributor.authorGhosh, Moumita
dc.contributor.authorGordon, Siamon
dc.contributor.authorLoper, Robyn
dc.contributor.authorTaylor, Philip R
dc.contributor.authorAkira, Shizuo
dc.contributor.authorUematsu, Satoshi
dc.contributor.authorWilliams, David L
dc.contributor.authorLeslie, Christina C
dc.date.accessioned2021-10-08T07:22:52Z
dc.date.available2021-10-08T07:22:52Z
dc.date.issued2006
dc.description.abstractPhagocytosis of non-opsonized microorganisms by macrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A(2) is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the beta-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-beta-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C(4) production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2(-/-) macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-beta-D-glucan. The results suggest that cytosolic phospholipase A(2) activation triggered by the beta-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression.
dc.identifier.apacitationSuram, S., , Ghosh, M., Gordon, S., Loper, R., , ... Leslie, C. C. (2006). Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor. <i>The Journal of Biological Chemistry</i>, 281(9), 5506 - 5514. http://hdl.handle.net/11427/35012en_ZA
dc.identifier.chicagocitationSuram, Saritha, , Moumita Ghosh, Siamon Gordon, Robyn Loper, , Shizuo Akira, Satoshi Uematsu, David L Williams, and Christina C Leslie "Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor." <i>The Journal of Biological Chemistry</i> 281, 9. (2006): 5506 - 5514. http://hdl.handle.net/11427/35012en_ZA
dc.identifier.citationSuram, S., , Ghosh, M., Gordon, S., Loper, R., , Akira, S. & Uematsu, S. et al. 2006. Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor. <i>The Journal of Biological Chemistry.</i> 281(9):5506 - 5514. http://hdl.handle.net/11427/35012en_ZA
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.ris TY - Journal Article AU - Suram, Saritha AU - Brown, Gordon D AU - Ghosh, Moumita AU - Gordon, Siamon AU - Loper, Robyn AU - Taylor, Philip R AU - Akira, Shizuo AU - Uematsu, Satoshi AU - Williams, David L AU - Leslie, Christina C AB - Phagocytosis of non-opsonized microorganisms by macrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A(2) is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the beta-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-beta-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C(4) production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2(-/-) macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-beta-D-glucan. The results suggest that cytosolic phospholipase A(2) activation triggered by the beta-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression. DA - 2006 DB - OpenUCT DP - University of Cape Town IS - 9 J1 - The Journal of Biological Chemistry LK - https://open.uct.ac.za PY - 2006 SM - 0021-9258 SM - 1083-351X T1 - Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor TI - Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor UR - http://hdl.handle.net/11427/35012 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35012
dc.identifier.vancouvercitationSuram S, , Ghosh M, Gordon S, Loper R, , et al. Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor. The Journal of Biological Chemistry. 2006;281(9):5506 - 5514. http://hdl.handle.net/11427/35012.en_ZA
dc.language.isoeng
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceThe Journal of Biological Chemistry
dc.source.journalissue9
dc.source.journalvolume281
dc.source.pagination5506 - 5514
dc.source.urihttps://dx.doi.org/10.1074/jbc.M509824200
dc.subject.otherAnimals
dc.subject.otherArachidonic Acid
dc.subject.otherCandida albicans
dc.subject.otherCells, Cultured
dc.subject.otherCyclooxygenase 2
dc.subject.otherEicosanoids
dc.subject.otherEnzyme Activation
dc.subject.otherHumans
dc.subject.otherIntracellular Signaling Peptides and Proteins
dc.subject.otherLectins, C-Type
dc.subject.otherMacrophages, Peritoneal
dc.subject.otherMembrane Proteins
dc.subject.otherMice
dc.subject.otherMice, Inbred C57BL
dc.subject.otherMice, Knockout
dc.titleRegulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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