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

Almeida, Anderson Rodrigues de; Dantas, Andréa Tavares; Gonçalves, Maria Eduarda De Oliveira; Chêne, Charlotte; Jeljeli, Mohamed; Chouzenoux, Sandrine; Thomas, Marine; Cunha, Eudes Gustavo Constantino; Valadares, Lilian David de Azevêdo; Gomes, João Victor de Melo; Paula, Simão Kalebe Silva de; Pitta, Marina Galdino da Rocha; Pitta, Ivan da Rocha; Rêgo, Moacyr Jesus Barreto de Melo; Pereira, Michelly Cristiny; Duarte, Ângela Luzia Branco Pinto; Abdalla, Dulcinéia Saes Parra; Nicco, Carole; Batteux, Frédéric; Pitta, Maíra Galdino da Rocha

doi:10.1007/s10787-023-01296-9

Cited by 2 publications

(2 citation statements)

References 78 publications

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“…Concomitantly, intraperitoneal injections of LPSF/GQ-16 were administered to a hypochlorous acid (HOCl)-induced mouse model of SSc. Results showed that LPSF/GQ-16 not only influenced the PBMCs' production of IL-2, IL-4, IL-6, IL-17A, TNF, and IFN-γ, but also reduced skin thickening, downregulated biomarkers of skin and lung fibrosis, as well as decreased the activation of immune cells in the experimental model [8].…”

Section: Introductionmentioning

confidence: 97%

“…Subsequent exposure of dcSSc dermal fibroblasts to harvested supernatants resulted in decreased production of matrix metalloproteinase-1 (MMP-1) [7]. Targeting the immune responses can be a promising therapeutic approach, as recently shown in the work by de Almeida et al [8]. Isolated PBMCs from patients with SSc were subjected to stimulation with phytohemagglutinin (PHA) and treatment with LPSF/GQ-16, a thiazolidinediones derivative.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Innate and Acquired Immune Responses in Systemic Sclerosis Primary Peripheral Blood Mononuclear Cells (PBMCs)

Szabo,

Badii,

Gaál

et al. 2023

IJMS

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Chronic immune activation in systemic sclerosis is supported by the production of a plethora of cytokines with proven regulatory activities of the immune responses. This study aimed to explore PBMCs’ cytokine profiles in SSc patients versus controls, as well as to investigate the balance between pro- and anti-inflammatory cytokines in association with disease duration. PBMCs were isolated from 18 SSc patients and 17 controls and further subjected to in vitro stimulation with lipopolysaccharide and heat-killed Candida albicans. Cytokine production was measured after 24 h and 7 days, respectively, using ELISA kits for interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor (TNF), IL-10, IL-17, and interferon-gamma (IFN-gamma). IL-1 β, IL-6, and TNF levels were increased in SSc patients compared with healthy volunteers irrespective of the stimulus used. IL-1Ra and Il-17 concentrations were not statistically different between groups, even though a trend toward higher levels in patients compared with their matched controls was also observed. Most cytokines demonstrated a stable course with disease progression, except for IL-10 levels, which declined over time. In conclusion, the results of this pilot study reveal that in patients with SSc a persistently enhanced immune response is established and maintained regardless of stimulus or disease duration.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Enhanced Innate and Acquired Immune Responses in Systemic Sclerosis Primary Peripheral Blood Mononuclear Cells (PBMCs)

Szabo,

Badii,

Gaál

et al. 2023

IJMS

View full text Add to dashboard Cite

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The Novel Cytokine Interleukin-41/Meteorin-like Is Reduced in Diffuse Systemic Sclerosis

Freedman,

Schock,

O’Reilly

2024

Cells

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Systemic sclerosis (SSc) is an autoimmune connective tissue disease with a triad of features that include vascular abnormalities, inflammation and skin and lung fibrosis. At the core of the disease is the activation of myofibroblasts from quiescent fibroblasts and this can be modified by various cytokines. IL-41 is a recently described cytokine that was initially characterised as an adipokine as it was highly expressed in adipocytes and adipose tissue. However, it has recently been identified as being widely expressed and has immunomodulatory functions. This study examined the circulating levels of IL-41 and its expression in skin biopsies. We demonstrated significantly reduced levels of IL-41 in diffuse SSc that was also mirrored in the skin of SSc patients. AMPK has been proposed as a downstream target of IL-41, so we also measure mammalian target of rapamycin in skin and found that this is elevated in SSc patients. We speculate that IL-41 maybe an antifibrotic cytokine and its reduction may facilitate the activation of fibroblasts.

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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

Cited by 2 publications

References 78 publications

Enhanced Innate and Acquired Immune Responses in Systemic Sclerosis Primary Peripheral Blood Mononuclear Cells (PBMCs)

Enhanced Innate and Acquired Immune Responses in Systemic Sclerosis Primary Peripheral Blood Mononuclear Cells (PBMCs)

The Novel Cytokine Interleukin-41/Meteorin-like Is Reduced in Diffuse Systemic Sclerosis

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