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  • Title: Effect of lysed and non-lysed sickle red cells on the activation of NLRP3 inflammasome and LTB4 production by mononuclear cells.
    Author: Pitanga TN, Santana SS, Zanette DL, Guarda CC, Santiago RP, Maffili VV, Lima JB, Carvalho GQ, Filho JR, Ferreira JRD, Aleluia MM, Nascimento VML, Carvalho MOS, Lyra IM, Borges VM, Oliveira RR, Goncalves MS.
    Journal: Inflamm Res; 2021 Jul; 70(7):823-834. PubMed ID: 34196737.
    Abstract:
    OBJECTIVE AND DESIGN: This study tested the hypothesis that sickle red blood cell (SS-RBC) can induce inflammasome NLRP3 components gene expression in peripheral blood mononuclear cells (PBMCs) as well as interleukin-1β (IL-1β) and leukotriene B4 (LTB4) production. Additionally, we investigated the effect of hydroxyurea (HU) treatment in these inflammatory markers. METHODS: PBMCs from healthy donors (AA-PBMC) were challenged with intact and lysed RBCs from SCA patients (SS-RBC) and from healthy volunteers (AA-RBC). NLRP3, IL-1β, IL-18 and Caspase-1 gene expression levels were assessed by quantitative PCR (qPCR). IL-1β protein levels and LTB4 were measured by ELISA. RESULTS: We observed that lysed SS-RBC induced the expression of inflammasome NLRP3 components, but this increase was more prominent for CASP1 and IL18 expression levels. Moreover, we observed that intact SS-RBC induced higher production of IL-1β and LTB4 than lysed SS-RBC. Although SCA patients treated with HU have a reduction in NLRP3 gene expression and LTB4 production, this treatment did not modulate the expression of other inflammasome components or IL-1β production. CONCLUSIONS: Thus, our data suggest that caspase-1, IL-1β and IL-18 may contribute to the inflammatory status observed in SCA and that HU treatment may not interfere in this inflammatory pathway.
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