Activation of cytosolic phospholipase A2α in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2

Shahid Noor, Howard Goldfine, Dawn E. Tucker, Saritha Suram, Laurel L. Lenz, Shizuo Akira, Satoshi Uematsu, Milena Girotti, Joseph V. Bonventre, Kevin Breuel, David L. Williams, Christina C. Leslie

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A2 (cPLA2α). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (ΔhlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and ΔhlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and ΔhlyLM correlates with diminished MAPK activation. WTLM but not ΔhlyLM increases intracellular calcium, which is implicated in regulation of cPLA2α. Prostaglandin E2, prostaglandin I 2, and leukotriene C4 are produced by cPLA 2α+/+ but not cPLA2α-/- macrophages in response to WTLM and ΔhlyLM. Tumor necrosis factor (TNF)-α production is significantly lower in cPLA2α +/+ than in cPLA2α-/- macrophages infected with WTLM and ΔhlyLM. Treatment of infected cPLA 2α+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFα production to the level produced by cPLA 2α-/- macrophages implicating prostaglandins in TNFα down-regulation. Therefore activation of cPLA2α in macrophages may impact immune responses to L. monocytogenes.

Original languageEnglish (US)
Pages (from-to)4744-4755
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
StatePublished - Feb 22 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Noor, S., Goldfine, H., Tucker, D. E., Suram, S., Lenz, L. L., Akira, S., Uematsu, S., Girotti, M., Bonventre, J. V., Breuel, K., Williams, D. L., & Leslie, C. C. (2008). Activation of cytosolic phospholipase A2α in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2. Journal of Biological Chemistry, 283(8), 4744-4755. https://doi.org/10.1074/jbc.M709956200