head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2023, vol. 29, issue3
Subject Area: Medicine
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DOI: 10.5272/jimab.2023293.5108
Published online: 19 September 2023

Original article
J of IMAB. 2023 Jul-Sep;29(3):5108-5111
EFFECT OF SAHA AND C-JUN N-TERMINAL KINASE INHIBITOR ON THE INDUCIBLE MRNA EXPRESSION OF INTERLEUKIN-17
Boncho Grigorov1ORCID logoCorresponding Autoremail, Magdalena Platikanova2ORCID logo, Zlatka Dobreva1ORCID logo, Antonia Grigorova1ORCID logo, Spaska Stanilova1ORCID logo,
1)Department of Molecular Biology, Immunology and Medical Genetics, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria.
2)Department of Hygiene, Infectious Diseases and Epidemiology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria.

ABSTRACT:
Interleukin-17 (IL-17A) is a critical cytokine for immune defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. On the other hand, the inducible expression of many cytokine genes is regulated by the receptor-activated intracellular signaling pathways, including the JNK pathway, and different epigenetic mechanisms, including histone deacetylation by HDACs. We investigated the comparative effect of the HDACs inhibitor Suberoylanilide Hydroxamic Acid (SAHA) and an inhibitor of the JNK signaling pathway in the regulation of the inducible IL-17 expression at the mRNA level in PBMCs from healthy donors. For the detection of IL-17 mRNA transcripts was used qRT-PCR. We detected significantly increased levels of IL-17mRNA under the stimulation of the PBMC cultures with lipopolysaccharide (LPS) or C3 binding glycoprotein (C3bgp) in the presence of an inhibitor of the JNK transduction pathway. The inhibition of the JNK signaling pathway leads to the upregulation of the expression of IL-17mRNA. SAHA did not demonstrate a significant effect on the IL-17mRNA transcription compared to the inhibitor of the JNK pathway. In conclusion, we suppose that the synthesis of IL-17 mRNA is regulated by both the JNK transduction pathway and HDAC activity, but with different effects.

Keywords: IL-17 gene expression, JNK inhibitor, HDAC,

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Please cite this article as: Grigorov B, Platikanova M, Dobreva Z, Grigorova A, Stanilova S. Effect of SAHA and c-Jun N-terminal kinase inhibitor on the inducible mRNA expression of Interleukin-17. J of IMAB. 2023 Jul-Sep;29(3):5108-5111. [Crossref - 10.5272/jimab.2023293.5108]

Corresponding AutorCorrespondence to: Boncho Grigorov, PhD, Department Molecular Biology, Immunology & Medical Genetics, Medical Faculty, Trakia University; 11, Armeiska Str., 6000 Stara Zagora, Bulgaria; E-mail: boncho.g@gmail.com

REFERENCES:
1. Amatya N, Garg AV, Gaffen SL. IL-17 signaling: the Yin and the Yang. Trends Immunol. 2017 May;38(5):310-322. [PubMed]
2. Veldhoen M. Interleukin 17 is a chief orchestrator of immunity. Nat Immunol. 2017 May 18;18(6):612-21. [PubMed]
3. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763–76. [PubMed
4. McAleer JP, Kolls JK. Mechanisms controlling Th17 cytokine expression and host defense. J Leukoc Biol. 2011 Aug;90(2):263–70. [PubMed]
5. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A. 2001 Nov20;98(24):13681-6. [PubMed]
6. Dobreva ZG, Stanilova SA, Miteva LD. Differences in the inducible gene expression and protein production of IL-12p40, IL-12p70 and IL-23: involvement of p38 and JNK kinase pathways. Cytokine. 2008 Jul;43(1):76-82. [PubMed]
7. Dobreva ZG, Miteva LD, Stanilova SA. The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes. Immunopharmacol Immunotoxicol. 2009 Jun;31(2):195-201. [PubMed]
8. Conte M, De Palma R, Altucci L. HDAC inhibitors as epigenetic regulators for cancer immunotherapy. Int J Biochem Cell Biol. 2018 May;98:65-74. [PubMed]
9. Kroesen M, Gielen P, Brok IC, Armandari I, Hoogerbrugge PM, Adema GJ. HDAC inhibitors and immunotherapy; a double edged sword? Oncotarget. 2014 Aug 30;5(16):6558-72. [PubMed]
10. Halili MA, Andrews MR, Labzin LI, Schroder K, Matthias G, Cao C, et al. Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS. J Leukoc Biol. 2010 Jun;87(6):1103-14. [PubMed]
11. Zhelev ZD, Stanilova SA, Carpenter BG. Isolation, partial characterization and complement inhibiting activity of a new glycoprotein from Cuscuta europea. Biochem Biophys Res Commun. 1994 Jul 15;202(1):186-94. [PubMed]
12. Rosadini CV, Kagan JC. Early innate immune responses to bacterial LPS. Curr Opin Immunol. 2017 Feb;44:14-19. [PubMed]
13. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2:17023. [PubMed]
14. Lloberas J, Valverde-Estrella L, Tur J, Vico T, Celada A. Mitogen-Activated Protein Kinases and Mitogen Kinase Phosphatase 1: A Critical Interplay in Macrophage Biology. Front Mol Biosci. 2016 Jun 28;3:28. [PubMed]
15. McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity. 2014 Jul 17;41(1):36-48. [PubMed]
16. Hannemann N, Jordan J, Paul S, Reid S, Baenkler HW, Sonnewald S, et al. The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and Arginase-1 Expression in Macrophages. J Immunol. 2017 May 1;198(9):3605-3614. [PubMed]
17. Wu Q, Wu W, Jacevic V, Franca TCC, Wang X, Kuca K. Selective inhibitors for JNK signalling: a potential targeted therapy in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):574-583. [PubMed]
18. Schmitz F, Mages J, Heit A, Lang R, Wagner H. Transcriptional activation induced in macrophages by Toll like receptor (TLR) ligands: from expression profiling to a model of TLR signaling. Eur JImmunol. 2004 Oct;34(10):2863-2873. [PubMed
19. Göschl L, Preglej T, Boucheron N, Saferding V, Müller L, Platzer A, et al. Histone deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis. J Autoimmun. 2020 Mar;108:102379. [PubMed]
20. Yan B, Liu Y, Bai H, Chen M, Xie S, Li D, et al. HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies. Theranostics. 2017 Feb 23;7(4):1002-1009. [PubMed]

Received: 28 February 2023
Published online: 19 September 2023

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