Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell
| Autor: | Valma Maria Lopes Nascimento, Magda Oliveira Seixas Carvalho, Jonilson Berlink Lima, Valéria M. Borges, Rayra Pereira Santiago, Sanzio Silva Santana, Luiz Carlos Júnior Alcântara, Thassila Nogueira Pitanga, Dalila Luciola Zanette, Graziele Q. Carvalho, Caroline Conceição da Guarda, Ricardo Riccio Oliveira, Marilda Souza Goncalves, Vitor Valério Maffili |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Adolescent Immunology Interleukin-1beta Erythrocytes Abnormal Anemia Sickle Cell Biology Biochemistry Peripheral blood mononuclear cell Leukotriene B4 Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Interleukin-1 beta production NLR Family Pyrin Domain-Containing 3 Protein medicine Immunology and Allergy Humans Child Molecular Biology Nitrites Inflammation integumentary system Toll-Like Receptors Interleukin-18 Interleukin hemic and immune systems Inflammasome Hematology TLR2 030104 developmental biology Gene Expression Regulation Child Preschool TLR4 Leukocytes Mononuclear Interleukin 18 Female 030215 immunology medicine.drug |
| Zdroj: | Cytokine. 83 |
| ISSN: | 1096-0023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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