| First Author | Suram S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 7 | Pages | e69002 |
| PubMed ID | 23950842 | Mgi Jnum | J:204931 |
| Mgi Id | MGI:5543743 | Doi | 10.1371/journal.pone.0069002 |
| Citation | Suram S, et al. (2013) Cytosolic phospholipase A(2)alpha and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation. PLoS One 8(7):e69002 |
| abstractText | The role of Group IVA cytosolic phospholipase A2 (cPLA2alpha) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2alpha 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 TNFalpha was lower in C. albicans-stimulated cPLA2alpha(+/+) than cPLA2alpha(-/-) macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2alpha(+/+) than cPLA2alpha(-/-) macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2alpha(+/+) and cPLA2alpha(-/-) macrophages (3 h) was compared by microarray. cPLA2alpha(+/+) macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2alpha(-/-) macrophages (>/=2-fold, p<0.05). Several pro-inflammatory genes were expressed at lower levels (Tnfalpha, Cx3cl1, Cd40, Ccl5, Csf1, Edn1, CxCr7, Irf1, Irf4, Akna, Ifngamma, several IFNgamma-inducible GTPases). Genes that dampen inflammation (Socs3, Il10, Crem, Stat3, Thbd, Thbs1, Abca1) and genes involved in host defense (Gja1, Csf3, Trem1, Hdc) were expressed at higher levels in cPLA2alpha(+/+) macrophages. Representative genes expressed lower in cPLA2alpha(+/+) macrophages (Tnfalpha, 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 cPLA2alpha, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation. |
