PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt pathway in experimental autoimmune myocarditis

He, Chao; Zhao, Fayun; Xie, Xinwen; Liao, Yanchun; Song, Ying; Liu, Chunxiao; Wu, Yang; Wang, Yue; Liu, Donghui; Wang, Yan; Zou, Jun; Qi, Zhi

doi:10.1016/j.yexcr.2018.12.005

Cited by 40 publications

(32 citation statements)

References 42 publications

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“…Interestingly, FOXP3 expression remained unchanged after treatment with fenofibrate, suggesting that this drug mainly exerts its anti-inflammatory effects through the modulation of the pro-inflammatory branch. However, our results differ from those observed by Zhou et al (77), showing the ability of fenofibrate to promote in vitro differentiation of Treg cells and those by Chang et al (76), who show increased expression of FOXP3 in the hearts of rats with experimental autoimmune myocarditis, after fenofibrate treatment. This disagreement could be attributed to several factors, including the genetic background of mice used for these studies and the etiology of the pathological condition (autoimmune vs. infectious) analyzed.…”

Section: Discussioncontrasting

confidence: 99%

“…In this regard, the inhibition of in vitro differentiation of Th17 by fenofibrate treatment has been reported previously (75). Moreover, this inhibition has been shown to play a beneficial role in an experimental model of dextran-induced colitis (74) and in an experimental model of autoimmune myocarditis in mice and rats (76). Interestingly, FOXP3 expression remained unchanged after treatment with fenofibrate, suggesting that this drug mainly exerts its anti-inflammatory effects through the modulation of the pro-inflammatory branch.…”

Section: Discussionmentioning

confidence: 65%

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IL-10-Dependent and -Independent Mechanisms Are Involved in the Cardiac Pathology Modulation Mediated by Fenofibrate in an Experimental Model of Chagas Heart Disease

et al. 2020

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 65%

IL-10-Dependent and -Independent Mechanisms Are Involved in the Cardiac Pathology Modulation Mediated by Fenofibrate in an Experimental Model of Chagas Heart Disease

et al. 2020

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“…Recently, Th17 cell processes were verified to be closely related to the occurrence and development of atherosclerosis, and STAT3 is the key regulator of Th17 cell differentiation through IL-6 induction 121, 144. The combined stimulation of transforming growth factor (TGF)-β and IL-6 can initiate the differentiation of CD4+ T cells into Th17 cells in mice 145. IL-6 upregulates the expression of IL-21 through the STAT3 pathway, which then increases the expression of the IL-23 receptor and the retinoic acid-related orphan receptor (ROR)γt 146, 147.…”

Section: Physiopathological Roles Of Stat3 In Atherosclerosismentioning

confidence: 99%

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

et al. 2019

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Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

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“…It is an essential intracellular signaling pathway and closely related to cardiac hypertrophy. This pathway has a key role in cell survival, growth, and differentiation [4][5][6] .…”

mentioning

confidence: 99%

“…IL-6 and the family-related proteins play a critical role in development of cardiac hypertrophy and heart failure. Therefore, modulation of the IL6 /STAT signaling pathway represents an essential strategy for the treatment of 5FU-induced cardiac injury 5,7,8 . Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors.…”

mentioning

confidence: 99%

IL6/STAT Signaling Pathway and PPARα are Involved in Mediating the dose Dependent Cardioprotective Effect of Fenofibrate in 5-fluorouracil induced Cardiotoxicity

Refaie

Shehata

Bayoumi

et al. 2021

Preprint

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Purpose: Cardiotoxicity of anticancer drugs such as 5-fluorouracil (5FU) and anthracyclines is a major complication that challenges their clinical usefulness. There is a critical need for finding new protecting drugs to defense against these harmful side effects. Up till now, there are no studies evaluate the possible cardioprotective effects of fenofibrate (FEN) in 5FU-induced cardiotoxicity. So that, we aimed in current model to evaluate such effect of FEN and explore different mechanisms mediating it.Methods: we used FEN (25, 50,100 mg/kg/day) orally for 7days with induction of cardiotoxicity by intraperitoneal (i.p.) injection of 5FU (150 mg/kg) on 5th day. Results: current study showed that 5FU succeeded in induction of cardiotoxicity and manifested by significant elevation of cardiac enzymes, tissue malondialdehyde (MDA), interleukin 6 (IL6), signal transducer and activator of transcription 4(STAT4) and caspase 3 levels. Furthermore, 5FU group showed toxic histopathological changes of marked cardiac damage and significant decrease in reduced glutathione (GSH), total antioxidant capacity (TAC) and peroxisome proliferator activated receptor alpha (PPARα) expression. FEN could reverse 5FU-induced cardiotoxicity by different mechanisms including upregulation of PPARα, inhibition of IL6/STAT signaling pathway, anti-inflammatory, anti-apoptotic and anti-oxidant properties.Conclusion: FEN had a significant cardioprotective effect against 5FU induced cardiac damage.

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PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt pathway in experimental autoimmune myocarditis

Cited by 40 publications

References 42 publications

IL-10-Dependent and -Independent Mechanisms Are Involved in the Cardiac Pathology Modulation Mediated by Fenofibrate in an Experimental Model of Chagas Heart Disease

IL-10-Dependent and -Independent Mechanisms Are Involved in the Cardiac Pathology Modulation Mediated by Fenofibrate in an Experimental Model of Chagas Heart Disease

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

IL6/STAT Signaling Pathway and PPARα are Involved in Mediating the dose Dependent Cardioprotective Effect of Fenofibrate in 5-fluorouracil induced Cardiotoxicity

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