Top

Journal of Inflammation

Published in:

Open Access 01-12-2018 | Research

ZNF580 – a brake on Interleukin-6

Authors: Philipp Stenzel, Kaj Nagorsen, Jonathan Bernd, Ulrike Leppert, Andreas Zakrzewicz, Janine Berkholz

Published in: Journal of Inflammation | Issue 1/2018

Abstract

Background

Zinc finger protein 580 (ZNF580) was reported to modulate angiogenesis, endothelial homeostasis and blood pressure control. ZNF580 regulated genes include VEGF-A and IL-8. However, it is unknown if ZNF580 could play a role during inflammation. The aim of this study was to find out if ZNF580 affects the expression of IL-6, if it occurs in monocytic cells and responds to inflammatory mediators.

Results

Overexpression of ZNF580 reduced LPS-induced promotor activity of IL-6. Consistently, overexpression of ZNF580 reduced by half the LPS-induced expression of IL-6. ZNF580 was strongly expressed in the nucleus of MonoMac6, a human monocytic cell line. LPS-stimulated IL-6 secretion increased when ZNF580 was suppressed with siRNA. After stimulation of MonoMac6 with LPS for 24 h, ZNF580 negatively correlated with the amount of secreted IL-6. In response to LPS, ZNF580 was increased within the first 8 h, followed by a marked decrease after 16 h. This decrease coincided with sustained IL-6 production.

Conclusion

This study demonstrated that ZNF580 inhibits LPS-induced expression of IL-6. ZNF580 was highly expressed in monocytic cells and therefore may contribute to the modulation of its IL-6 production, at least in response to LPS. This suggests cooperation between ZNF580 and NFκB, which could play a role during sepsis.

Zhang W, Chen B, Zeng W, Wu GXH. Cloning and tissue expression of a novel gene down-regulated by low density lipoprotein. Basic Med Sci Clin. 2003;23:279–82.

Sun H-Y, Wei S-P, Xu R-C, Xu P-X, Zhang W-C. Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: novel insights into angiogenesis. Biochem Biophys Res Commun Elsevier Inc. 2010;395(3):361–6. https://doi.org/10.1016/j.bbrc.2010.04.019.CrossRef

Luo Y, Hu W, Xu R, Hou B, Zhang L, Zhang W. ZNF580 a novel C2H2 zinc-finger transcription factor, interacts with the TGF-β signal molecule Smad2. Cell Biol Int. 2011;35(11):1153–7. https://doi.org/10.1042/CBI20110050.CrossRefPubMed

Luo Y, Zhao Y, Li X, Zhao J, Zhang W. ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGFβ1/ALK5/Smad2 pathway. Mol Cell Biochem. 2014;393(1–2):199–207.CrossRefPubMed

Hao X, Li Q, Lv J, Yu L, Ren X, Zhang L, Feng Y, Zhang W. CREDVW-linked polymeric micelles as a targeting gene transfer vector for selective transfection and proliferation of endothelial cells. ACS Appl Mater Interfaces. 2015;7(22):12128–40. https://doi.org/10.1021/acsami.5b02399.CrossRefPubMed

Shi C, Yao F, Li Q, Khan M, Ren X, Feng Y, Huang J, Zhang W. Regulation of the endothelialization by human vascular endothelial cells by ZNF580 gene complexed with biodegradable microparticles. Biomaterials. 2014;35(25):7133–45. https://doi.org/10.1016/j.biomaterials.2014.04.110.CrossRefPubMed

Li Q, Shi C, Zhang W, Behl M, Lendlein A, Feng Y. Nanoparticles complexed with gene vectors to promote proliferation of human vascular endothelial cells. Advanced Healthcare Materials. 2015;4(8):1225–35. https://doi.org/10.1002/adhm.201400817.CrossRefPubMed

Hoffmann CJ, Hohberg M, Chlench S, Maroski J, Drab M, Siegel G, Pries AR, Zakrzewicz A. Suppression of zinc finger protein 580 by high oxLDL/LDL-ratios is followed by enhanced expression of endothelial IL-8. Atherosclerosis. 2011;216(1):103–8. https://doi.org/10.1016/j.atherosclerosis.2011.01.017.CrossRefPubMed

Ren D, Wang H, Liu J, Zhang M, Zhang W. ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation. Mol Cell Biochem. 2012;359(1–2):183–91. https://doi.org/10.1007/s11010-011-1013-0.CrossRef

10.

Ziegler-Heitbrock HW, Thiel E, Fütterer A, Herzog V, Wirtz A, Riethmüller G. Establishment of a human cell line (mono mac 6) with characteristics of mature monocytes. Int J Cancer. 1988;41(3):456–61.CrossRefPubMed

11.

Serbina NV, Jia T, Hohl TM, Pamer EG. Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol. 2008;26:421–52. https://doi.org/10.1146/annurev.immunol.26.021607.090326.CrossRefPubMedPubMedCentral

12.

Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11(11):762–74. https://doi.org/10.1038/nri3070.CrossRefPubMedPubMedCentral

13.

Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, Hauschildt S. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol. 2011;31(5):379–446.CrossRefPubMed

14.

Eddy J-B. Care Medicine Cellular mechanisms in Sepsis. J Intensive Care Med. 2007;22(2):63–72.CrossRef

15.

Uusitalo-Seppälä R, Koskinen P, Leino A, Peuravuori H, Vahlberg T, Rintala EM. Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin and interleukin-6. Scand J Infect Dis. 2011;43(11–12):883–90. https://doi.org/10.3109/00365548.2011.600325.CrossRefPubMed

16.

Jekarl DW, Lee SY, Lee J, Park YJ, Kim Y, Park JH, Wee JH, Choi SP. Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis. 2013;75(4):342–7. https://doi.org/10.1016/j.diagmicrobio.2012.12.011.CrossRefPubMed

17.

Alspach E, Flanagan KC, Luo X, Ruhland MK, Huang H, Pazolli E, Donlin MJ, Marsh T, Piwnica-Worms D, Monahan J, Novack DV, McAllister SS, Stewart S. A. p38MAPK plays a crucial role in stromal mediated tumorigenesis. Cancer Discov. 2014. https://doi.org/10.1158/2159-8290.CD-13-0743 PubMed 24670723.CrossRefPubMedPubMedCentral

18.

Roach JC, Smith KD, Strobe KL, Nissen SM, Haudenschild CD, Zhou D, Vasicek TJ, Held GA, Stolovitzky GA, Hood LE, Aderem A. Transcription factor expression in lipopolysaccharide- activated peripheralblood-derived mononuclear cells. Proc Natl Acad Sci U S A. 1993;104(41):16245–50.CrossRef

19.

Cordle SR, Donald R, Read MA, Hawigers J. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Re1 and related NF-KB proteins in human Monocytic THP-1. J Biol Chem. 1993;268(5):11803–10.PubMed

20.

Razin SV, Borunova VV, Maksimenko OG, Kantidze OL. Cys2His2 zinc finger protein family: classification, functions, and major members. Biochemist. 2012;77(3):217–26. https://doi.org/10.1134/S0006297912030017.CrossRef

Title: ZNF580 – a brake on Interleukin-6
Authors: Philipp Stenzel
Kaj Nagorsen
Jonathan Bernd
Ulrike Leppert
Andreas Zakrzewicz
Janine Berkholz
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Inflammation / Issue 1/2018
Electronic ISSN: 1476-9255
DOI: https://doi.org/10.1186/s12950-018-0196-5

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

ACC 2024 Congress

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients

Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis

MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α

Anti-inflammatory effect of hesperidin enhances chondrogenesis of human mesenchymal stem cells for cartilage tissue repair

Caspase recruitment domain (CARD) family (CARD9, CARD10, CARD11, CARD14 and CARD15) are increased during active inflammation in patients with inflammatory bowel disease