Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell.

Autor: Pitanga TN; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil; Instituto de Ciências da Saúde (ICS), Universidade Federal da Bahia (UFBA), 40110902 Salvador, Bahia, Brazil., Oliveira RR; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Zanette DL; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Guarda CC; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Santiago RP; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Santana SS; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Nascimento VML; Fundação de Hematologia e Hemoterapia da Bahia (HEMOBA), 40286240 Salvador, Bahia, Brazil., Lima JB; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Carvalho GQ; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Maffili VV; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Carvalho MOS; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil; Hospital Universitário Professor Edgard Santos (HUPES), UFBA, 40110060 Salvador, Bahia, Brazil., Alcântara LCJ; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Borges VM; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil., Goncalves MS; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz - FIOCRUZ/BA, 40296710 Salvador, Bahia, Brazil; Faculdade de Farmácia, UFBA, 40170115 Salvador, Bahia, Brazil. Electronic address: mari@bahia.fiocruz.br.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2016 Jul; Vol. 83, pp. 75-84. Date of Electronic Publication: 2016 Apr 02.
DOI: 10.1016/j.cyto.2016.03.016
Abstrakt: This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1β, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1β were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1β and IL-18 expression and induced IL-1β, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: