Details

Autor(en) / Beteiligte

• 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

Titel

PPARγ partial agonist LPSF/GQ-16 prevents dermal and pulmonary fibrosis in HOCl-induced systemic sclerosis (SSc) and modulates cytokine production in PBMC of SSc patients

Ist Teil von

• Inflammopharmacology, 2024-02, Vol.32 (1), p.433-446

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Graphical abstract