title: Plasmodium falciparum: effect of antimalarial drugs, malaria pigment (β-haematin) and Plasmodium falciparum lysate on monocyte GTP-cyclohydrolase 1 gene expression.
abstract: In interferon-γ activated human macrophages, GTP-cyclohydrolase 1 catalyses the conversion of guanosine triphosphate to 7,8-dihydroneopterin triphosphate, which is dephosphorylated and oxidized to form neopterin. Elevated levels of neopterin have been detected in the urine and serum of malaria-infected patients. In this study, U937 cells were treated with interferon-γ and one of the following antimalarial drugs: amodiaquine, artemisinin, chloroquine, doxycycline, primaquine, pyrimethamine or quinine. The effects of treating the U937 cells with malaria pigment (β-haematin), latex beads, or Plasmodium falciparum-infected-red blood cell lysates were also investigated. U937 GTP-cyclohydrolase 1 mRNA expression was monitored using reverse-transcriptase-quantitative PCR. Artemisinin, primaquine, and quinine down-regulated GTP-cyclohydrolase 1 gene expression 1.26-, 1.29-, and 1.63-fold, respectively. The remaining drugs had insignificant effects. β-haematin up-regulated GTP-cyclohydrolase 1 mRNA expression 1.18-fold, whereas P. falciparum-infected red blood cell lysate down-regulated expression 1.56-fold. These results show the differing immunomodulatory actions of antimalarial drugs and malaria pigment taking place in monocytes.
authors.affiliation: Department of Biochemistry, School of Biochemistry, Genetics and Microbiology, University of KwaZulu-Natal, Pietermaritzburg Campus, Private Bag X01, Scottsville 3209, South Africa.
authors.forename: Bridgette M
authors.initials: BM
authors.lastname: Cumming
authors.forename: Gregory M F
authors.initials: GM
authors.lastname: Watson
authors.forename: J P Dean
authors.initials: JP
authors.lastname: Goldring
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology; D006136:GTP Cyclohydrolase / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006420:Hemeproteins / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008863:Microspheres; D009000:Monocytes / Q000201:enzymology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D012333:RNA, Messenger; C020753:hemozoin; D007371:Interferon-gamma; D006136:GTP Cyclohydrolase