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Reports outline falciparum malaria study findings from Pennsylvania State University, Medical Department
2009 AUG 3 - (NewsRx.com) -- "Proinflammatory responses induced by Plasmodium falciparum glycosylphosphatidylinositols (GPIs) are thought to be involved in malaria pathogenesis. In this study, we investigated the role of MAPK-activated protein kinase 2 (MK2) in the regulation of tumor necrosis factor-alpha(TNF-alpha) and interleukin (IL)12, two of the major inflammatory cytokines produced by macrophages stimulated with GPIs," researchers in the United States report. "We show that MK2 differentially regulates the GPI-induced production of TNF-alpha and IL-12. Although TNF-alpha production was markedly decreased, IL-12 expression was increased by 2-3-fold in GPI-stimulated MK2(-/-) macrophages compared with wild type (WT) cells. MK2(-/-) macrophages produced markedly decreased levels of TNF-alpha than WT macrophages mainly because of lower mRNA stability and translation. In the case of IL-12, mRNA was substantially higher in MK2(-/-) macrophages than WT. This enhanced production is due to increased NF-kappa B binding to the gene promoter, a markedly lower level expression of the transcriptional repressor factor c-Maf, and a decreased binding of GAP-12 to the gene promoter in MK2(-/-) macrophages. Thus, our data demonstrate for the first time the role of MK2 in the transcriptional regulation of IL-12. Using the protein kinase inhibitors SB203580 and U0126, we also show that the ERK and p38 pathways regulate TNF-alpha and IL-12 production, and that both inhibitors can reduce phosphorylation of MK2 in response to GPIs and other toll-like receptor ligands," wrote J.Z. Zhu and colleagues, Pennsylvania State University, Medical Department. The researchers concluded: "These results may have important implications for developing therapeutics for malaria and other infectious diseases.." Zhu and colleagues published their study in the Journal of Biological Chemistry (MAPK-activated Protein Kinase 2 Differentially Regulates Plasmodium falciparum Glycosylphosphatidylinositol-induced Production of Tumor Necrosis Factor-alpha and Interleukin-12 in Macrophages. Journal of Biological Chemistry, 2009;284(23):15750-15761). For additional information, contact D.C. Gowda, Pennsylvania State University, College Medical, Dept. of Biochemistry & Molecular Biology, 500 University Dr., Hershey, PA 17033, USA. Publisher contact information for the Journal of Biological Chemistry is: American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. Keywords: United States, Hershey, Falciparum Malaria, Biological Chemistry, Cytokines, Enzyme Research, Kinase, Malaria, Necrosis, Plasmodium falciparum, Tropical Disease, Pennsylvania State University, Medical Department. This article was prepared by Malaria Weekly editors from staff and other reports. Copyright 2009, Malaria Weekly via NewsRx.com.
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