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Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2020, vol. 26, issue2
Subject Area: Medicine
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DOI: 10.5272/jimab.2020262.3127
Published online: 14 May 2020
Original article
J of IMAB. 2020 Apr-Jun;26(2):3127-3132
INFLUENCE OF AN INHIBITOR OF JNK ON THE SECRETION OF THE INFLAMMASOME–DEPENDENT PROINFLAMMATORY CYTOKINES
Boncho Grigorov1
, Spaska Stanilova1, Magdalena Platikanova2, Zlatka Dobreva1,
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:
Purpose: In this study, we determine the influence of prolonged exposure on organic air pollutants, on the secretion of inflammasome-dependent cytokines IL-1β and IL-18. We also investigate the involvement of the JNK signalling pathway in the inducible IL-1β and IL-18 secretion.
Materials and Methods: PBMC from healthy individuals working in an environment with organic particulate matter pollution and healthy donors working in an environment without pollution were isolated by density gradient centrifugation. The isolated cells were stimulated with LPS and C3bgp with or without SP600125, a selective JNK inhibitor and cultured for 6 h. After cell supernatants harvesting, ELISA tests were performed for IL-1β and IL-18 mature protein quantification.
Results: The results showed that individuals working in a polluted environment secreted significantly higher levels of the biologically active IL-1β and IL-18 compared to individuals working in a non-polluted environment. We found that SP600125 inhibited the secretion of the mature form of both cytokines in the two groups - individuals with pollution and individuals without pollution significantly.
Conclusion: Environmental pollution with organic particulate matter leads to increased IL-1β and IL-18 secretion from peripheral immune cells. JNK transduction pathway is involved in the secretion of the biologically active form of IL-1β and IL-18, after stimulation. We suppose that individuals working in a polluted environment are predisposed to the development of inflammatory or autoimmune/allergic disorders, mediated by the permanent inflammasome activation. The inhibition of the JNK signalling pathway may be beneficial for the treatment of the condition mediated by the increased inflammasome-dependent proinflammatory cytokine secretion.
Keywords: IL-1β, IL-18, inflammasome, JNK, SP600125,
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Please cite this article as: Grigorov B, Stanilova S, Platikanova M, Dobreva Z. Influence of an inhibitor of JNK on the secretion of the inflammasome–dependent proinflammatory cytokines. J of IMAB. 2020 Apr-Jun;26(2):3127-3132. DOI: 10.5272/jimab.2020262.3127
Correspondence to: Boncho Grigorov, PhD, Department Molecular Biology, Immunology & Medical Genetics, Medical Faculty, Trakia University, Stara Zagora; 11 Armeiska Str., BG-6000, Stara Zagora, Bulgaria; E-mail: boncho.g@gmail.com
REFERENCES:
1. 1. Kohka H, Nishibori M, Iwagaki H,Nakaya N, Yoshino T,Kobashi K, et al. Histamine Is a Potent Inducer of IL-18 and IFN-g in Human Peripheral Blood Mononuclear Cells. J Immunol. 2000 Jun 15;164(12):6640-6. [PubMed] [Crossref]
2. Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002 Sep 1;20(5; SUPP/27):S1-3. [PubMed]
3. Buchs ND, Di Giovine FS, Silvestri T, Vannier E, Duff GW, and Miossec P. IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels. Genes and immunity. 2001 Jun;2(4):222-8. [PubMed]
4. Phani S, Loike JD, and Przedborski S. Neurodegeneration and inflammation in Parkinson’s disease. Parkinsonism & related disorders. 2012 Jan 1;18:S207-9. [PubMed] [Crossref]
5. Yosipovitch G, Shohat B, Bshara J, Wysenbeek A, Weinberger A. Elevated serum interleukin 1 receptors and interleukin 1B in patients with Behcet’s disease: correlations with disease activity and severity. Isr J Med Sci. 1995 Jun;31(6):345-8. [PubMed]
6. Dinarello CA. Overview of the IL-1 Family in Innate Inflammation and Acquired Immunity. Immunol Rev. 2018 Jan;281(1):8-27. [PubMed] [Crossref]
7. Kawakami K, Qureshi MH, Zhang T, Okamura H, Kurimoto M, andSaito AJ. IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-g production. J Immunol. 1997 Dec 1;159(11):5528-34. [PubMed]
8. Kobayashi K, Kai M, Gidoh M, Nakata N, Endoh M, Singh RP, et al. The possible role of interleukin (IL)-12 and interferon-ginducing factor/IL-18 in protection against experimental Mycobacterium leprae infection in mice. ClinImmunol Immunopathol. 1998 Sep 1;88(3):226-31. [PubMed] [Crossref]
9. Rothe H, Jenkins NA, Copeland NG, and Kolb H. Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2. J Clin Invest. 1997 Feb 1;99(3):469-74. [PubMed]
10. Arican O, Aral M, Sasmaz S, andCiragil P. Serum levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005;2005(5):273-9. [PubMed] [Crossref]
11. Monteleone G, Trapasso F, Parrello T, Biancone L, Stella A, Iuliano R, et al. Bioactive IL-18 expression is up-regulated in Crohn’s disease. JImmunol. 1999 Jul 1;163(1):143-7. [PubMed]
12. Amerio P, Frezzolini A, Abeni D, Teofoli P, Girardelli CR, O De P, et al. Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines. Clin Exp Rheumatol. 2002;20(4):535-8. [PubMed]
13. Van de Veerdonk FL, Netea MG, Dinarello CA, andJoosten LA. Inflammasome activation and IL-1β and IL-18 processing during infection. TrendsImmunol. 2011 Mar 1;32(3):110-6. [PubMed] [Crossref]
14. Jo EK, Kim JK, Shin DM, Sasakawa C. Molecular Mechanisms Regulating NLRP3 Inflammasome Activation. Cell Mol Immunol. 2016 Mar;13(2):148-59. [PubMed] [Crossref]
15. 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 Nov 20;98(24):13681-6. [PubMed] [Crossref]
16. Wagner EF, Nebreda BR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nature Rev Cancer. 2009 Aug;9(8):537-49. [PubMed]
17. Dobreva ZG, Stanilova SA. The immunomodulatory activity of C3 binding glycoprotein (C3bgp) is mediated by the complement receptor type III and mitogen-activated protein kinase signal transduction pathways. ImmunopharmacolImmunotoxicol. 2007 Jan 1;29(3-4):549-62. [PubMed] [Crossref]
18. 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 1;43(1):76-82. [PubMed] [Crossref]
19. 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. ImmunopharmacolImmunotoxicol. 2009 Jun 1;31(2):195-201. [PubMed] [Crossref]
20. Zhelev Z, Stanilova S, Carpenter B. Isolation, partial characterization and complement inhibiting activity of a new glycoprotein from Cuscutaeuropea. BiochemBiophys Res Commun. 1994 Jul 15;202(1):186-94. [PubMed] [Crossref]
21. Poole JA, and Romberger DJ. Immunological and Inflammatory Responses to Organic Dust inAgriculture. CurrOpin Allergy ClinImmunol. 2012 Apr;12(2):126. [PubMed]
22. Neumann K, Ruland J. Kinases conquer the inflammasomes. Nat Immunol. 2013 Dec;14(12):1207. [PubMed]
23. Hara H, Tsuchiya K, Kawamura I, Fang R, Hernandez-Cuellar E, Shen Y, et al. Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity. Nat Immunol. 2013 Dec;14(12):1247. [PubMed]
24. Chen H, Yang D, Han F, Tan J, Zhang L, Xiao J, et al. The Bacterial T6SS Effector EvpP Prevents NLRP3 Inflammasome Activation by Inhibiting the Ca2+-Dependent MAPK-Jnk Pathway. Cell Host & Microbe. 2017 Jan 11;21(1):47-58. [PubMed] [Crossref]
25. Li Q, Zhang X, Wang W, Li LL, Xu Q, Wu X, et al. CPT-11 activates NLRP3 inflammasome through JNK and NF-κBsignalings. Toxicol Appl Pharmacol. 2015 Dec 1;289(2):133-41. [PubMed] [Crossref].
Received: 25 June 2019
Published online: 14 May 2020