| Autor: |
de Almeida, Anderson Rodrigues, Dantas, Andréa Tavares, de Oliveira Gonçalves, Maria Eduarda, Chêne, Charlotte, Jeljeli, Mohamed, Chouzenoux, Sandrine, Thomas, Marine, Cunha, Eudes Gustavo Constantino, de Azevedo Valadares, Lilian David, de Melo Gomes, João Victor, de Paula, Simão Kalebe Silva, da Rocha Pitta, Marina Galdino, da Rocha Pitta, Ivan, de Melo Rêgo, Moacyr Jesus Barreto, Pereira, Michelly Cristiny, Duarte, Angela Luzia Branco Pinto, Abdalla, Dulcineia Saes Parra, Nicco, Carole, Batteux, Frédéric, da Rocha Pitta, Maira Galdino |
| Předmět: |
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| Zdroj: |
Inflammopharmacology; Feb2024, Vol. 32 Issue 1, p433-446, 14p |
| Abstrakt: |
Thiazolidinediones (TZD) are synthetic molecules that have a range of biological effects, including antifibrotic and anti-inflammatory, and they may represent a promising therapeutic strategy for systemic sclerosis (SSc). The aim of this study was to investigate the immunomodulatory and antifibrotic properties of LPSF/GQ-16, a TZD derivative, in peripheral blood mononuclear cells (PBMC) from SSc patients and in a murine model of SSc HOCl-induced. The PBMC of 20 SSc patients were stimulated with phytohemagglutinin (PHA) and treated with LPSF/GQ-16 for 48 h, later cytokines in the culture supernatants were quantified by sandwich enzyme-linked immunosorbent assay (ELISA) or cytometric bead array (CBA). Experimental SSc was induced by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. HOCl-induced SSc mice received daily treatment with LPSF/GQ-16 (30 mg/kg) through intraperitoneal injections during the same period. Immunological parameters were evaluated by flow cytometry and ELISA, and dermal and pulmonary fibrosis were evaluated by RT-qPCR, hydroxyproline dosage and histopathological analysis. In PBMC cultures, it was possible to observe that LPSF/GQ-16 modulated the secretion of cytokines IL-2 (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.001), IL-17A (p = 0.006), TNF (p < 0.001) and IFN-γ (p < 0.001). In addition, treatment with LPSF/GQ-16 in HOCl-induced SSc mice promoted a significant reduction in dermal thickening (p < 0.001), in the accumulation of collagen in the skin (p < 0.001), down-regulated the expression of fibrosis markers in the skin (Col1a1, α-Sma and Tgfβ1, p < 0.001 for all) and lungs (Il4 and Il13, p < 0.001 for both), as well as reduced activation of CD4 + T cells (p < 0.001), B cells (p < 0.001) and M2 macrophages (p < 0.001). In conclusion, LPSF/GQ-16 showed immunomodulatory and antifibrotic properties, demonstrating the therapeutic potential of this molecule for SSc. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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