Duarte A.L.B.P.,Federal University of Pernambuco |
Dantas A.T.,Federal University of Pernambuco |
Dantas A.T.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
De Ataide Mariz H.,Federal University of Pernambuco |
And 7 more authors.
Molecular Biology Reports | Year: 2013
The immunological role of interleukin 27 has been reported in various inflammatory diseases, but its importance in systemic lupus erythematosus pathogenesis is not completely established. The aim of this study was to evaluate serum levels of IL-27 in SLE patients and its correlation with clinical manifestations and disease activity. IL-27 levels were assessed in 70 SLE patients and 30 healthy controls by ELISA. Clinical and laboratory parameters were recorded. Statistic analyzes were performed by Graph Prism 3.02 software. The IL-27 serum levels were significantly decreased in SLE patients compared with controls (mean 899.92 and 1,531.22 pg/ml, P = 0.0005). There was a correlation between IL-27 levels and C3 levels (P = 0.004). Nevertheless, there was no association of serum IL-27 levels with disease activity evaluated by SLEDAI score (P = 0.9605). No significant difference was found regarding IL-27 levels between SLE patients with and without nephritis, haematuria, proteinuria and positive anti-dsDNA. Correlation analysis between serum IL-27 levels and SLEDAI, SLICC, proteinuria levels, C4 and CH50 levels also showed no association. These data demonstrated decreased serum levels of IL-27 in SLE patients but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. © 2013 Springer Science+Business Media Dordrecht.
Rego M.J.B.D.M.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
Galdino-Pitta M.R.,Federal University of Pernambuco |
Pereira D.T.M.,Federal University of Pernambuco |
Da Silva J.C.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
And 6 more authors.
Medicinal Chemistry Research | Year: 2014
Thiazolidinediones are known to have antidiabetic activity, but new activities are being discovered every year; among these, their anticancer activity has received the most attention. In this study, we synthesized three new disubstituted thiazolidinediones and assayed their cytotoxicity against six tumor cell lines, as well as against normal cells. Cytometry studies and molecular modeling were also performed to elucidate the mechanism of cytotoxicity. Of the three new thiazolidinediones synthesized, (5Z)-5-(3-bromo-benzylidene)-3-(4-nitrobenzyl)-thiazolidine-2,4-dione (LPSF/SF-13) exhibited the most promising activity; it was selectively cytotoxic against leukemia, lymphoma, glioblastoma, and hepatocarcinoma cell lines without being toxic to normal cells. Apoptosis was the main cell death process induced by this compound, although it also induced necrosis. Furthermore, molecular modeling studies showed that LPSF/SF-13 had good affinity for peroxisome proliferator-Activated receptor γ; binding to the receptor involved hydrogen bonds with Arg288 and Ser342 residues (bond distances of 3.1 and 2.8 Å, respectively), as well as a π-bonding interaction with His449. We concluded that LPSF/SF-13 is a promising compound for in vivo and combination therapy studies against cancer. © 2014 Springer Science+Business Media New York.
Da Rocha Junior L.F.,Federal University of Pernambuco |
Da Rocha Junior L.F.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
De Melo Rego M.J.B.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
Cavalcanti M.B.,Laboratorio Of Imunomodulacao E Novas Abordagens Terapeuticas Linat |
And 9 more authors.
BioMed Research International | Year: 2013
Rheumatoid arthritis (RA) is an autoimmune disease frequently characterized by chronic synovitis of multiple joints. The pathogenesis of RA is complex and involves many proinflammatory cytokines as Th17 related ones. PPARγ is a nuclear receptor activator that represses proinflammatory gene expression. Thus, this work aimed to synthetize a new thiazolidinedione (TZD) analogue based on a well-known anti-inflammatory and PPARγ agonist activity of this ring and evaluate its anti-inflammatory activity. After chemical structure confirmation, the compound named 5-(5-bromo-2-methoxy-benzylidene)-3-(2-nitro-benzyl)- thiazolidine-2,4-dione TM17 was submitted to cytokine releasing inhibition and PPARγ genetic modulation assays. The new compound showed no toxicity on human and murine cells, decreasing IL-6 secretion by murine splenocytes and reducing IL-17A, IL-22, and IFN-γ expression in peripheral blood mononuclear cells from patients with RA. TM17 was more efficient in modulating the mRNA expression of PPARγ than its well-used TZD agonist rosiglitazone. Surprisingly, TM17 was efficient on IL-17A and IFN-γ reduction, like the positive control methylprednisolone, and presented a better effect on IL-22 levels. In conclusion, PBMCs obtained from RA patients under TM17 treatment present a significant reduction in IL-17A, IL-22, and IFN-γ levels, but not IL-6 when compared with nontreated cells, as well as increase PPARγ mRNA expression in absence of stimulus addressing it as a promising molecule in RA treatment. © 2013 Laurindo Ferreira da Rocha Junior et al.