ArticleArteriosclerosis, thrombosis, and vascular biology2018
IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14).
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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78citing papers in PubMed, 1 pooled it
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- The Shared IL-12/IL-35 p35 Subunit Is Associated With Heightened Atherogenic Risk in African Patients With Type 2 Diabetes.Endocrinology, diabetes & metabolism · 2026Article
- Integrative Omics Analysis Reveals a CD206Barrier immunity · 2026Article
- HBO1 suppresses anti-tumor immunity of CD8⁺ T Cells in thyroid cancer by recruiting BRD4 to regulate VTCN1 expression.Cancer immunology, immunotherapy : CII · 2026Article
- Anti-Inflammatory Interleukins in the Pathogenesis of Atherosclerosis.International journal of molecular sciences · 2026Review
- A new paradigm: 46 structural cell types function as environment-supporting innate immune cells, with endothelial and vascular smooth muscle cells as key prototypes.iNew medicine · 2026Article
- Novel Organelle-Based Intracellular Immunity with Mechanistic and Therapeutic Implications.Barrier immunity · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- New Types of Post-Translational Modification of Proteins in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- H3K14la drives endothelial dysfunction in sepsis-induced ARDS by promoting SLC40A1/transferrin-mediated ferroptosis.MedComm · 2025Article
- The recombinant IL-35 and anti-Ebi3 antibody administration before implantation modulate immune regulation and fetal outcomes in an abortion-prone mouse model.Frontiers in immunology · 2025Article
- H3K14: A histone site closely related to diseases.Journal of Cancer · 2025Review
- Genetic variant rs2243115 of the IL-12/IL-35 pathway contributes to the risk of coronary artery disease.International journal of medical sciences · 2025Article
- Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4International journal of drug discovery and pharmacology · 2024Article
- Decreased Expression of IL-35 and Its Receptor Contributes to Impaired Megakaryopoiesis in the Pathogenesis of Immune Thrombocytopenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.Pharmacology & therapeutics · 2024Review
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- The Effects of Nicotine and Cannabinoids on Cytokines.Current pharmaceutical design · 2024Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Xinyuan LiFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Ying ShaoFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Xiaojin ShaFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Pu FangFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Yin-Ming KuoFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Andrew J AndrewsFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Yafeng LiFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
William Y YangFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Massimo MaddaloniFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
David W PascualFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Jin J LuoFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Xiaohua JiangFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Hong WangFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.).
Xiaofeng YangFrom the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cancer Biology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (Y.-M.K., A.J.A.); and Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville (M.M., D.W.P.). xfyang@temple.edu.
Temple University Health System · USFox Chase Cancer Center · US
Funding
The Role of Histone Chaperones in Histone Acetylation and Nucleosome DynamicsR01GM102503 · NIGMS · UNIVERSITY OF NORTH CAROLINA WILMINGTON · PI ANDREWS, ANDREW JOSEPH · 2014 to 2023
$3.9MCD40 monocyte in chronic kidney diseaseR01DK113775 · NIDDK · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2017 to 2021
$3.3MHyperhomocysteinemia and HDL MetabolismR01HL117654 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2013 to 2017
$3.0MCaspase-1 activation mediates chronic kidney disease-accelerated atherosclerosisR01HL131460 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI CHOI, ERIC T., WANG, HONG · 2016 to 2019
$2.8MThe roles of miR-155 in regulating atherosclerosis and metabolically healthy obesityR01HL138749 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.6MNADHP Oxidase-mediated MC differentiation & Endothelial Dysfunction in HHcyR01HL110764 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2011 to 2015
$2.5MAtherogenic roles of complement systemR01HL130233 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI QIN, XUEBIN, WANG, HONG · 2016 to 2019
$2.5MIL-35 suppression of endothelial cell activation and atherosclerosisR01HL132399 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.3MHHcy-induced Inflammatory Monocyte and Macrophage Differentiation in DiabetesR01DK104116 · NIDDK · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2015 to 2019
$2.2MNHLBI NIH HHS R01 HL110764NHLBI NIH HHS R01 HL117654NHLBI NIH HHS R01 HL130233NHLBI NIH HHS R01 HL131460NHLBI NIH HHS R01 HL132399NHLBI NIH HHS R01 HL138749NIDDK NIH HHS R01 DK104116NIDDK NIH HHS R01 DK113775NIGMS NIH HHS R01 GM102503
Abstract
objectiveIL-35 (interleukin-35) is an anti-inflammatory cytokine, which inhibits immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. It remains unknown whether atherogenic stimuli induce IL-35 and whether IL-35 inhibits atherogenic lipid-induced endothelial cell (EC) activation and atherosclerosis. EC activation induced by hyperlipidemia stimuli, including lysophosphatidylcholine is considered as an initiation step for monocyte recruitment and atherosclerosis. In this study, we examined the expression of IL-35 during early atherosclerosis and the roles and mechanisms of IL-35 in suppressing lysophosphatidylcholine-induced EC activation. APPROACH AND
resultsUsing microarray and ELISA, we found that IL-35 and its receptor are significantly induced during early atherosclerosis in the aortas and plasma of ApoE (apolipoprotein E) knockout mice-an atherosclerotic mouse model-and in the plasma of hypercholesterolemic patients. In addition, we found that IL-35 suppresses lysophosphatidylcholine-induced monocyte adhesion to human aortic ECs. Furthermore, our RNA-sequencing analysis shows that IL-35 selectively inhibits lysophosphatidylcholine-induced EC activation-related genes, such as ICAM-1 (intercellular adhesion molecule-1). Mechanistically, using flow cytometry, mass spectrometry, electron spin resonance analyses, and chromatin immunoprecipitation-sequencing analyses, we found that IL-35 blocks lysophosphatidylcholine-induced mitochondrial reactive oxygen species, which are required for the induction of site-specific H3K14 (histone 3 lysine 14) acetylation, increased binding of proinflammatory transcription factor AP-1 in the promoter of ICAM-1, and induction of ICAM-1 transcription in human aortic EC. Finally, IL-35 cytokine therapy suppresses atherosclerotic lesion development in ApoE knockout mice.
conclusionsIL-35 is induced during atherosclerosis development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation-AP-1-mediated EC activation.
Indexed as
AcetylationAnimalsAortaAortic DiseasesAtherosclerosisCells, CulturedDisease Models, AnimalEndothelial CellsFemaleHistonesHumansIntercellular Adhesion Molecule-1InterleukinsLysineLysophosphatidylcholinesMaleHistonesICAM1 protein, humanIntercellular Adhesion Molecule-1interleukin-35, humaninterleukin-35, mouseinterleukin 35 receptor, mouseInterleukinsLysineLysophosphatidylcholinesReactive Oxygen SpeciesReceptors, InterleukinTranscription Factor AP-1atherosclerosisendothelial cellshyperlipidemiamitochondriareactive oxygen species
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