ArticleMolecular medicine (Cambridge, Mass.)
Reduced peripheral PGE2 biosynthesis in Plasmodium falciparum malaria occurs through hemozoin-induced suppression of blood mononuclear cell cyclooxygenase-2 gene expression via an interleukin-10-independent mechanism.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Distinct cytokine profiles in malaria coinfections: A systematic review.PLoS neglected tropical diseases · 2023Pooled it
- Reduced systemic bicyclo-prostaglandin-E2 and cyclooxygenase-2 gene expression are associated with inefficient erythropoiesis and enhanced uptake of monocytic hemozoin in children with severe malarial anemia.American journal of hematology · 2012Trial
- The roles of COX-2 in protozoan infection.Frontiers in immunology · 2023Review
- Ingestion of hemozoin by peripheral blood mononuclear cells alters temporal gene expression of ubiquitination processes.Biochemistry and biophysics reports · 2022Article
- Hemozoin: a Complex Molecule with Complex Activities.Current clinical microbiology reports · 2021Article
- L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria.Scientific reports · 2019Article
- Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: Implications for leukocyte inhibitory signalling.EBioMedicine · 2019Article
- The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children.Malaria journal · 2017Article
- Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation.Molecular medicine (Cambridge, Mass.) · 2016Article
- Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response.Anemia · 2016Review
- Anopheles gambiae eicosanoids modulate Plasmodium berghei survival from oocyst to salivary gland invasion.Memorias do Instituto Oswaldo Cruz · 2014Article
- Hemozoin inhibition and control of clinical malaria.Advances in pharmacological sciences · 2014Review
- Suppressed circulating bicyclo-PGE2 levels and leukocyte COX-2 transcripts in children co-infected with P. falciparum malaria and HIV-1 or bacteremia.Biochemical and biophysical research communications · 2013Article
- Relationship between inflammatory mediator patterns and anemia in HIV-1 positive and exposed children with Plasmodium falciparum malaria.American journal of hematology · 2012Article
- Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells.Placenta · 2011Article
- Mechanisms of erythropoiesis inhibition by malarial pigment and malaria-induced proinflammatory mediators in an in vitro model.American journal of hematology · 2011Article
- Severe malarial anemia: innate immunity and pathogenesis.International journal of biological sciences · 2011Review
- Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2.Malaria journal · 2010Article
- A novel functional variant in the stem cell growth factor promoter protects against severe malarial anemia.Infection and immunity · 2010Article
- Suppression of a novel hematopoietic mediator in children with severe malarial anemia.Infection and immunity · 2009Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Molecular immunologic determinants of disease severity during Plasmodium falciparum malaria are largely undetermined. Our recent investigations showed that peripheral blood mononuclear cell (PBMC) cyclooxygenase-2 (COX-2) gene expression and plasma prostaglandin E(2) (PGE(2)) production are suppressed in children with falciparum malaria relative to healthy, malaria-exposed children with partial immunity. Furthermore, decreased COX-2/PGE(2) levels were significantly associated with increased plasma interleukin-10 (IL-10), an anti-inflammatory cytokine that inhibits the expression of COX-2 gene products. To determine the mechanism(s) responsible for COX-2-derived PGE(2) suppression, PBMCs were cultured from children with falciparum malaria. PGE(2) production was suppressed under baseline and COX-2-promoting conditions (stimulation with lipopolysaccharide [LPS] and interferon [IFN]-gamma) over prolonged periods, suggesting that an in vivo-derived product(s) was responsible for reduced PGE(2) biosynthesis. Ingestion of hemozoin (malarial pigment) by PBMC was investigated as a source of COX-2/PGE(2) suppression in PBMCs from healthy, malaria-naive adults. In addition, synthetically prepared hemozoin, beta-hematin, was used to investigate the effects of the core iron component of hemozoin, ferriprotoporphyrin-IX (FPIX). Physiologic concentrations of hemozoin or b-hematin suppressed LPS- and IFN-gamma-induced COX-2 mRNA in a time- and dose-dependent manner, resulting in decreased COX-2 protein and PGE(2) production. Suppression of COX-2/PGE(2) by hemozoin was not due to decreased cell viability as evidenced by examination of mitochondrial bioactivity. These data illustrate that ingestion of FPIX by blood mononuclear cells is responsible for suppression of COX-2/PGE(2). Although hemozoin induced overproduction of IL-10, neutralizing IL-10 antibodies failed to restore PGE(2) production. Thus, acquisition of hemozoin by blood mononuclear cells is responsible for suppression of PGE(2) in malaria through inhibition of de novo COX-2 transcripts via molecular mechanisms independent of increased IL-10 production.
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