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  • Poster presentation
  • Open Access

Haemozoin enhances MMP-9 production through MAPK p38-dependent mechanisms in human adherent monocytes

  • 1,
  • 2,
  • 2 and
  • 1
Malaria Journal201413 (Suppl 1) :P73

https://doi.org/10.1186/1475-2875-13-S1-P73

  • Published:

Keywords

  • Malaria
  • MAPK Phosphorylation
  • Complicated Malaria
  • Basal Phosphorylation
  • Malarial Pigment

In human adherent monocytes matrix metalloproteinase-9 (MMP-9) expression and secretion is upregulated by the lipid moiety of natural haemozoin (nHz, malarial pigment). A role for 15-(S, R)-hydroxy-6, 8, 11, 13-eicosatetraenoic acid (15-HETE), a nHZ lipoperoxidation product, has been suggested. Here, the underlying mechanisms were investigated, focusing on the involvement of mitogen-activated protein kinases (MAPKs). Either early or late p38 MAPK phosphorylation was induced by nHz, which did not modify basal phosphorylation and expression ratios of extracellular signal-regulated kinase-1/2 and c-jun N-terminal kinase-1/2. 15-HETE mimicked nHZ effects on p38 MAPK. Lipid-free synthetic (s)HZ and delipidized (d)HZ did not. Both nHZ and 15-HETE promoted the phosphorylation of MAPK-activated protein kinase-2, a known substrate of p38 MAPK. Such an effect was abolished by SB203580 (synthetic p38 MAPK inhibitor). SB203580 also abrogated the nHZ-dependent and 15-HETE-dependent enhancement of MMP-9 mRNA and protein levels in cell lysates and supernatants. These data suggest that nHZ and 15-HETE upregulate MMP-9 expression and secretion through the activation of p38 MAPK pathway in human adherent monocytes. This work provides new evidence on the mechanisms underlying MMP-9 deregulation in malaria. These data might help to design new specific drugs for adjuvant therapy in complicated malaria.

Authors’ Affiliations

(1)
Dipartimento di Neuroscienze, Università di Torino, Torino, Italy
(2)
Dipartimento di Oncologia, Università di Torino, Torino, Italy

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