IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14)

Li, Xinyuan; Shao, Ying; Sha, Xiaojin; Pu, Fang; Kuo, Yin-Ming; Andrews, Andrew J.; Li, Yafeng; Yang, William Y.; Maddaloni, Massimo; Pascual, David W.; Luo, Jin Jun; Jiang, Xiaohua; Wang, Hong; Yang, Xiaofeng

doi:10.1161/atvbaha.117.310626

Cited by 87 publications

(109 citation statements)

References 58 publications

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“…Contrary to clinical experiments, as an anti-inflammatory cytokine, IL-35 expression in mouse atherosclerotic plaques was significantly increased . A small number of other studies, however, have reported increased IL-35 expression in atherosclerotic plaques and serum in ApoE mice fed with a high-fat diet, as well as in the plasma of patients with coronary artery disease (Gorzelak-Pabiś et al, 2017;Li et al, 2018). Using a mouse model of atherosclerosis, administration of recombinant mouse IL-35 significantly decreased plaque area in the aortic root, and Treg immune responses were also found to be enhanced (Tao et al, 2016).…”

Section: Animal Studiesmentioning

confidence: 94%

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Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Wang

et al. 2020

Front. Pharmacol.

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Cardiovascular diseases represent a complex group of clinical syndromes caused by a variety of interacting pathological factors. They include the most extensive disease population and rank first in all-cause mortality worldwide. Accumulating evidence demonstrates that cytokines play critical roles in the presence and development of cardiovascular diseases. Interleukin-12 family members, including IL-12, IL-23, IL-27 and IL-35, are a class of cytokines that regulate a variety of biological effects; they are closely related to the progression of various cardiovascular diseases, including atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction, and acute cardiac injury. This paper mainly discusses the role of IL-12 family members in cardiovascular diseases, and the molecular and cellular mechanisms potentially involved in their action in order to identify possible intervention targets for the prevention and clinical treatment of cardiovascular diseases.

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Section: Animal Studiesmentioning

confidence: 94%

“…81760051 to YL). Lee et al, 1999;Davenport and Tipping, 2003;Hauer et al, 2005;Koltsova et al, 2012;Hirase et al, 2013;Wang et al, 2014;Subramanian et al, 2015;Tao et al, 2016;Gorzelak-Pabiś et al, 2017;Engelbertsen et al, 2018;Fatkhullina et al, 2018;Li et al, 2018;Ryu et al, 2018;Huang et al, 2019;Wang et al, 2019…”

Section: Fundingmentioning

confidence: 99%

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Wang

et al. 2020

Front. Pharmacol.

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“…IL-35 has been identified as a functional cytokine of regulatory T cells. IL-35 plays an anti-inflammatory role and ameliorates atherosclerosis [ 15 ], autoimmune disease [ 16 ], autoimmune diabetes [ 17 ], arthritis [ 18 , 19 ], and explosive hepatitis [ 20 ]. The biological effects of IL-12 and IL-35 were abrogated when the IL-12p35 subunit was knocked out.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice

Huang

et al. 2018

EBioMedicine

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Background Recent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms. Methods First, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before treatment with DOX. Results DOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptotic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy. Conclusions IL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words).

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“…IL-35 protected against acute liver and kidney injury caused by LPS through inhibiting inflammatory responses (27,28). IL-35 also inhibited lysophosphatidylcholine-induced mitochondrial reactive oxygen species (mtROS) production and human aortic endothelial activation (29,30). Furthermore, IL-35 was reported to exert anti-apoptotic effects that prevent diabetic neuropathic pain and doxorubicin-induced cardiac injury (24,31).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrosis

et al. 2020

Preprint

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Previous studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury remains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by

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IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14)

Abstract: IL-35 is induced during atherosclerosis development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation-AP-1-mediated EC activation.

Cited by 87 publications

References 58 publications

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrosis

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