Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

Saritha Suram; Lori J. Silveira; Spencer Mahaffey; Gordon D. Brown; Joseph V. Bonventre; David L. Williams; Neil A. R. Gow; Donna L. Bratton; Robert C. Murphy; Christina C. Leslie

doi:10.1371/journal.pone.0069002

Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

Saritha Suram, Lori J. Silveira, Spencer Mahaffey, Gordon D. Brown, Joseph V. Bonventre, David L. Williams, Neil A. R. Gow, Donna L. Bratton, Robert C. Murphy, Christina C. Leslie

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

4 Downloads (Pure)

Abstract

The role of Group IVA cytosolic phospholipase A₂ (cPLA₂α) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA₂α releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E₂ and leukotriene C₄ were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNFα was lower in C. albicans-stimulated cPLA₂α^+/+ than cPLA₂α^-/- macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA₂α^+/+ than cPLA₂α^-/- macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA₂α^+/+ and cPLA₂α^-/- macrophages (3 h) was compared by microarray. cPLA₂α^+/+ macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA₂α^-/- macrophages (≥2-fold, p2α^+/+ macrophages. Representative genes expressed lower in cPLA₂α^+/+ macrophages (Tnfα, Csf1) were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA₂α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.

Original language	English
Article number	e69002
Pages (from-to)	1-17
Number of pages	17
Journal	PloS ONE
Volume	8
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0069002
Publication status	Published - 25 Jul 2013

Bibliographical note

Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis.

Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Access to Document

10.1371/journal.pone.0069002Licence: CC BY

Cytosolic Phospholipase A 2 α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation
© 2013 Suram et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 1.35 MBLicence: CC BY

Cite this

Suram, S., Silveira, L. J., Mahaffey, S., Brown, G. D., Bonventre, J. V., Williams, D. L., Gow, N. A. R., Bratton, D. L., Murphy, R. C., & Leslie, C. C. (2013). Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation. PloS ONE, 8(7), 1-17. Article e69002. https://doi.org/10.1371/journal.pone.0069002

@article{9288e9734dd14918aa591799adc230fe,

title = "Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation",

abstract = "The role of Group IVA cytosolic phospholipase A2 (cPLA2α) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2α releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNFα was lower in C. albicans-stimulated cPLA2α+/+ than cPLA2α-/- macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2α+/+ than cPLA2α-/- macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2α+/+ and cPLA2α-/- macrophages (3 h) was compared by microarray. cPLA2α+/+ macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2α-/- macrophages (≥2-fold, p2α+/+ macrophages. Representative genes expressed lower in cPLA2α+/+ macrophages (Tnfα, Csf1) were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA2α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.",

author = "Saritha Suram and Silveira, {Lori J.} and Spencer Mahaffey and Brown, {Gordon D.} and Bonventre, {Joseph V.} and Williams, {David L.} and Gow, {Neil A. R.} and Bratton, {Donna L.} and Murphy, {Robert C.} and Leslie, {Christina C.}",

note = "Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis. Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

year = "2013",

month = jul,

day = "25",

doi = "10.1371/journal.pone.0069002",

language = "English",

volume = "8",

pages = "1--17",

journal = "PloS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "7",

}

TY - JOUR

T1 - Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

AU - Suram, Saritha

AU - Silveira, Lori J.

AU - Mahaffey, Spencer

AU - Brown, Gordon D.

AU - Bonventre, Joseph V.

AU - Williams, David L.

AU - Gow, Neil A. R.

AU - Bratton, Donna L.

AU - Murphy, Robert C.

AU - Leslie, Christina C.

N1 - Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis. Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2013/7/25

Y1 - 2013/7/25

N2 - The role of Group IVA cytosolic phospholipase A2 (cPLA2α) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2α releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNFα was lower in C. albicans-stimulated cPLA2α+/+ than cPLA2α-/- macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2α+/+ than cPLA2α-/- macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2α+/+ and cPLA2α-/- macrophages (3 h) was compared by microarray. cPLA2α+/+ macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2α-/- macrophages (≥2-fold, p2α+/+ macrophages. Representative genes expressed lower in cPLA2α+/+ macrophages (Tnfα, Csf1) were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA2α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.

AB - The role of Group IVA cytosolic phospholipase A2 (cPLA2α) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2α releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNFα was lower in C. albicans-stimulated cPLA2α+/+ than cPLA2α-/- macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2α+/+ than cPLA2α-/- macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2α+/+ and cPLA2α-/- macrophages (3 h) was compared by microarray. cPLA2α+/+ macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2α-/- macrophages (≥2-fold, p2α+/+ macrophages. Representative genes expressed lower in cPLA2α+/+ macrophages (Tnfα, Csf1) were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA2α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.

UR - http://www.scopus.com/inward/record.url?scp=84880817676&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0069002

DO - 10.1371/journal.pone.0069002

M3 - Article

C2 - 23950842

AN - SCOPUS:84880817676

SN - 1932-6203

VL - 8

SP - 1

EP - 17

JO - PloS ONE

JF - PloS ONE

IS - 7

M1 - e69002

ER -

Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this