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Role of 15-hydroxyeicosatetraenoic acid in hemozoin-induced lysozyme release from human adherent monocytes

Authors

  • Manuela Polimeni,

    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
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  • Elena Valente,

    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
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  • Elisabetta Aldieri,

    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
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  • Amina Khadjavi,

    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
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  • Giuliana Giribaldi,

    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
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  • Mauro Prato

    Corresponding author
    1. Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
    2. Dipartimento di Neuroscienze, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Torino, Italy
    • Dipartimento di Neuroscienze, Università di Torino, Corso Raffaello 30, Torino10125, Italy
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    • Tel.: +39-011-790-8198; Fax: +39-011-790-8174


Abstract

Natural hemozoin (nHZ), a lipid-bound ferriprotoporphyrin IX crystal produced by Plasmodium parasites after hemoglobin catabolism, seriously compromises the functions of human monocytes, and 15-hydroxyeicosatetraenoic acid (15-HETE) and 4-hydroxynonenal (4-HNE), two nHZ lipoperoxidation products, have been related to such a functional impairment. nHZ was recently shown to promote inflammation-mediated lysozyme release from human monocytes through p38 mitogen-activated protein kinase- (MAPK)- and nuclear factor (NF)-κB-dependent mechanisms. This study aimed at identifying the molecule of nHZ lipid moiety that was responsible for these effects. Results showed that 15-HETE mimicked nHZ effects on lysozyme release, whereas 4-HNE did not. 15-HETE-enhanced lysozyme release was abrogated by anti-TNF-α and anti-IL-1β-blocking antibodies and mimicked by recombinant cytokines; on the contrary, MIP-1α/CCL3 was not involved as a soluble mediator of 15-HETE effects. Moreover, 15-HETE early activated p38 MAPK and NF-κB pathways by inducing p38 MAPK phosphorylation; cytosolic I-κBα phosphorylation and degradation; NF-κB nuclear translocation and DNA-binding. Inhibition of both routes through chemical inhibitors (SB203580, quercetin, artemisinin, and parthenolide) prevented 15-HETE-dependent lysozyme release. Collectively, these data suggest that 15-HETE plays a major role in nHZ-enhanced monocyte degranulation. © 2013 BioFactors, 2013

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