{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T16:11:17Z","timestamp":1762445477369,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"intramural funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and\/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10\/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p\/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.<\/jats:p>","DOI":"10.3390\/ijms25073719","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T13:39:56Z","timestamp":1711546796000},"page":"3719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-7876","authenticated-orcid":false,"given":"Christof","family":"Ulrich","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"},{"name":"KfH Nierenzentrum, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Herberger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeynep","family":"Canim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Markau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-0847","authenticated-orcid":false,"given":"Matthias","family":"Girndt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"},{"name":"KfH Nierenzentrum, 06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/ejcn.2016.49","article-title":"Unraveling the relationship between mortality, hyponatremia, inflammation and malnutrition in hemodialysis patients: Results from the international MONDO initiative","volume":"70","author":"Dekker","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/sdi.12024","article-title":"Fluid overload and inflammation\u2014A vicious cycle","volume":"26","author":"Raimann","year":"2013","journal-title":"Semin. Dial."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1053\/j.jrn.2018.06.005","article-title":"Interactions between Malnutrition, Inflammation, and Fluid Overload and Their Associations with Survival in Prevalent Hemodialysis Patients","volume":"28","author":"Dekker","year":"2018","journal-title":"J. Ren. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ulrich, C., Wilke, A., Schleicher, N., Girndt, M., and Fiedler, R. (2020). Hypervolemia-Induced Immune Disturbances Do Not Involve IL-1\u00df but IL-6 and IL-10 Activation in Haemodialysis Patients. Toxins, 12.","DOI":"10.3390\/toxins12030159"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1001\/jamacardio.2021.3079","article-title":"Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome","volume":"6","author":"Batra","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5414\/CN108778","article-title":"Volume overload and its risk factors in South African chronic kidney disease patients: An appraisal of bioimpedance spectroscopy and inferior vena cava measurements","volume":"86","author":"Hassan","year":"2016","journal-title":"Clin. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/HYPERTENSIONAHA.111.173328","article-title":"Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage","volume":"59","author":"Zhang","year":"2012","journal-title":"Hypertension"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1152\/physrev.00031.2016","article-title":"Role of the Immune System in Hypertension","volume":"97","author":"Pons","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12727","DOI":"10.1111\/sji.12727","article-title":"The roles of SOCS3 and STAT3 in bacterial infection and inflammatory diseases","volume":"88","author":"Gao","year":"2018","journal-title":"Scand. J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0092-8674(95)90311-9","article-title":"Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation","volume":"82","author":"Wen","year":"1995","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"112313","DOI":"10.1016\/j.yexcr.2020.112313","article-title":"Noncanonical pS727 post translational modification dictates major STAT3 activation and downstream functions in breast cancer","volume":"396","author":"Dimri","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155059","DOI":"10.1016\/j.cyto.2020.155059","article-title":"STAT3-driven hematopoiesis and lymphopoiesis abnormalities are dependent on serine phosphorylation","volume":"130","author":"Balic","year":"2020","journal-title":"Cytokine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.4049\/jimmunol.170.3.1383","article-title":"Suppressor of cytokine signaling 1 inhibits IL-10-mediated immune responses","volume":"170","author":"Ding","year":"2003","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41577-019-0125-8","article-title":"The aryl hydrocarbon receptor: An environmental sensor integrating immune responses in health and disease","volume":"19","author":"Rothhammer","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.kint.2017.11.010","article-title":"Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease","volume":"93","author":"Dou","year":"2018","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.3389\/fimmu.2018.02033","article-title":"Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway","volume":"9","author":"Zhu","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.4049\/jimmunol.1701670","article-title":"eIF4E-Binding Proteins 1 and 2 Limit Macrophage Anti-Inflammatory Responses through Translational Repression of IL-10 and Cyclooxygenase-2","volume":"200","author":"William","year":"2018","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1182\/blood-2010-12-325647","article-title":"Targeting of microRNA-142-3p in dendritic cells regulates endotoxin-induced mortality","volume":"117","author":"Sun","year":"2011","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1002\/art.34505","article-title":"Decreased microRNA-142-3p\/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus","volume":"64","author":"Ding","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ulrich, C., Canim, Z., Herberger, E., Girndt, M., and Fiedler, R. (2023). Inflammation in Hypervolemic Hemodialysis Patients: The Roles of RelB and Caspase-4. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417550"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/ndt\/gfac275","article-title":"Bioimpedance in CKD: An untapped resource?","volume":"38","author":"Mayne","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Antlanger, M., Josten, P., Kammer, M., Exner, I., Lorenz-Turnheim, K., Eigner, M., Paul, G., Klauser-Braun, R., Sunder-Plassmann, G., and S\u00e4emann, M.D. (2017). Blood volume-monitored regulation of ultrafiltration to decrease the dry weight in fluid-overloaded hemodialysis patients: A randomized controlled trial. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0639-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000487106","article-title":"Estimating of Residual Kidney Function by Multi-Frequency Bioelectrical Impedance Analysis in Hemodialysis Patients Without Urine Collection","volume":"43","author":"Beberashvili","year":"2018","journal-title":"Kidney Blood Press. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3000605211031063","DOI":"10.1177\/03000605211031063","article-title":"Effect of bioimpedance-defined overhydration parameters on mortality and cardiovascular events in patients undergoing dialysis: A systematic review and meta-analysis","volume":"49","author":"Wang","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/1744-9987.12750","article-title":"Relationship Between Leptin Level, Inflammation, and Volume Status in Maintenance Hemodialysis Patients","volume":"23","year":"2019","journal-title":"Ther. Apher. Dial."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.bcp.2008.11.021","article-title":"AHR-mediated immunomodulation: The role of altered gene transcription","volume":"77","author":"Kerkvliet","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/glia.22805","article-title":"Aryl hydrocarbon receptor mediates both proinflammatory and anti-inflammatory effects in lipopolysaccharide-activated microglia","volume":"63","author":"Lee","year":"2015","journal-title":"Glia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39638","DOI":"10.1074\/jbc.M106286200","article-title":"Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necrosis factor-alpha and lipopolysaccharide","volume":"276","author":"Ke","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/S0006-2952(01)00859-0","article-title":"Role of cytokines in the lipopolysaccharide-evoked depression of cytochrome P450 in the brain and liver","volume":"62","author":"Nicholson","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1042\/BST0341028","article-title":"STAT3-mediated anti-inflammatory signalling","volume":"34","author":"Murray","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2016.05.001","article-title":"STAT3 signaling in immunity","volume":"31","author":"Hillmer","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fimmu.2012.00020","article-title":"SOCS, Inflammation, and Autoimmunity","volume":"3","author":"Yoshimura","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.4049\/jimmunol.170.6.3263","article-title":"Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3","volume":"170","author":"Niemand","year":"2003","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3389\/fimmu.2014.00058","article-title":"SOCS3, a Major Regulator of Infection and Inflammation","volume":"5","author":"Carow","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/ni938","article-title":"IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages","volume":"4","author":"Yasukawa","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_38","first-page":"145","article-title":"The role of microRNAs in the control and mechanism of action of IL-10","volume":"380","author":"Quinn","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41419-019-1565-6","article-title":"Blockade of miR-142-3p promotes anti-apoptotic and suppressive function by inducing KDM6A-mediated H3K27me3 demethylation in induced regulatory T cells","volume":"10","author":"Gao","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1172\/JCI123839","article-title":"miR-142 controls metabolic reprogramming that regulates dendritic cell activation","volume":"129","author":"Sun","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1189\/jlb.1A1014-519RR","article-title":"Regulation of miR-24, miR-30b, and miR-142-3p during macrophage and dendritic cell differentiation potentiates innate immunity","volume":"98","author":"Fordham","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"NP50","DOI":"10.1177\/0145561319847972","article-title":"Mir-142-3p Regulates Inflammatory Response by Contributing to Increased TNF-\u03b1 in Chronic Rhinosinusitis with Nasal Polyposis","volume":"100","author":"Qing","year":"2021","journal-title":"Ear Nose Throat J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000526902","article-title":"Diagnosis of Fluid Overload: From Conventional to Contemporary Concepts","volume":"12","author":"Koratala","year":"2022","journal-title":"Cardiorenal Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/ki.2013.434","article-title":"Estimation of fluid volumes in hemodialysis patients: Comparing bioimpedance with isotopic and dilution methods","volume":"85","author":"Piccoli","year":"2014","journal-title":"Kidney Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3719\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:15Z","timestamp":1760105955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073719"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073719","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,3,27]]}}}