title: Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-κB in Macrophages.
abstract: Hemozoin (Hz) is released from ruptured erythrocytes during malaria infection caused byPlasmodiumsp., in addition the malaria infected individuals are prone to bacterial sepsis. The molecular interactions between Hz, bacterial components and macrophages remains poorly investigated. In this report, we investigated the combinatorial immune-modulatory effects of phagocytosed Hz, Interferon gamma (IFNγ) or lipopolysaccharide (LPS) in macrophages. Macrophages were treated with various concentrations of commercial synthetic Hz, and surprisingly it did not result in inducible nitric oxide synthase (iNOS) expression. However, when macrophages were pretreated with Hz and then challenged with IFNγ or LPS, there was a differential impact on iNOS expression. There was an increase in iNOS expression when macrophages were pre-treated with Hz and subsequently treated with IFNγ when compared to IFNγ alone. Whereas iNOS expression was reduced when Hz phagocytosed macrophages were stimulated with LPS compared to LPS alone. Furthermore, there was an increased activation of NF-κB in Hz phagocytosed macrophages that were challenged with IFNγ. The interaction between Hz and macrophages has an impact on iNOS expression.
authors: Department of Medicine, University of Illinois, Chicago, Illinois, USA.
authors: Ravi
authors: R
authors: Ranjan
authors: Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep, The Ohio State University, Columbus, Ohio, USA.
authors: Manjula
authors: M
authors: Karpurapu
authors: Department of Medicine, University of Illinois, Chicago, Illinois, USA.
authors: Asha
authors: A
authors: Rani
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, USA.
authors: Athar H
authors: AH
authors: Chishti
authors: Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep, The Ohio State University, Columbus, Ohio, USA.
authors: John W
authors: JW
authors: Christman
keywords: Hemozoin; Inducible nitric oxide synthase; Lipopolysaccharide; Macrophage; Malaria; Sepsis