Evaluation of Interleukin-32 and cyclooxygenase-2 expression in HAM/TSP patients and HTLV-1 asymptomatic carriers

Document Type : Original Article

Authors

1 Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

5 Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disorder associated with HTLV-1. Cytokines and inflammatory mediators have a major role in forming inflammation in HAM/TSP patients. This study aimed to measure the levels of IL-32, a proinflammatory cytokine associated with autoinflammatory disorders, and also cyclooxygenase -2 (COX-2) as a key mediator of inflammatory pathways in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs).
Materials and Methods: Peripheral blood monocyte cells (PBMCs) were isolated from HAM/TSP patients, ACs, and healthy controls (HCs), and DNA and RNA were extracted to evaluate HTLV-1 proviral load (PVL) and expression of IL-32 and COX-2, using real-time PCR. Serum levels of IL-32 were determined by using an ELISA assay.
Results: The expression level of IL-32 was significantly higher in ACs compared with HAM/TSP patients and HCs (p 0.05, respectively). There were no statistically significant differences in the expression levels of Cox-2 and protein levels of IL-32 between the study groups.  HTLV-1 PVL was higher in HAM/TSP patients compared with ACs.
Conclusion:  Results showed increased mRNA levels of IL-32 in ACs. Since HTLV-1 PVL in ACs is lower than in HAM/TSP patients, it could be concluded that IL-32 might be an HTLV-1 inhibitor that seems to control virus replication. Despite the difference in IL-32 mRNA levels between study groups, no statistically significant differences were observed in IL-32 serum levels. Also, there were no significant differences in COX-2 expression.

Keywords

References

1. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, et al. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 1985; 2:407-410.
2. Gessain A, Cassar O. Epidemiological aspects and world distribution of htlv-1 infection. Front Microbiol 2012; 3:388.
3. Rafatpanah H, Hedayati-Moghaddam MR, Fathimoghadam F, Bidkhori HR, Shamsian SK, Ahmadi S, et al. High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey. J Clin Virol 2011; 52:172-176.
4. Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A 1982; 79:2031-2035.
5. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, et al. HTLV-I associated myelopathy, a new clinical entity. Lancet 1986; 1:1031-1032.
6. Vakili R, Sabet F, Aahmadi S, Boostani R, Rafatpanah H, Shamsian A, et al. Human T-lymphotropic virus type I (HTLV-I) proviral load and clinical features in iranian HAM/TSP patients: Comparison of HTLV-I proviral load in HAM/TSP patients. Iran J Basic Med Sci 2013; 16:268-272.
7. Horiuchi I, Kawano Y, Yamasaki K, Minohara M, Furue M, Taniwaki T, et al. Th1 dominance in HAM/TSP and the optico-spinal form of multiple sclerosis versus Th2 dominance in mite antigen-specific IgE myelitis. J Neurol Sci 2000; 172:17-24.
8. Fuzii HT, da Silva Dias GA, de Barros RJ, Falcao LF, Quaresma JA. Immunopathogenesis of HTLV-1-assoaciated myelopathy/tropical spastic paraparesis (HAM/TSP). Life Sci 2014; 104:9-14.
9. Kim S. Interleukin-32 in inflammatory autoimmune diseases. Immune Netw 2014; 14:123-127.
10. Lee S, Kim JH, Kim H, Kang JW, Kim SH, Yang Y, et al. Activation of the interleukin-32 pro-inflammatory pathway in response to human papillomavirus infection and over-expression of interleukin-32 controls the expression of the human papillomavirus oncogene. Immunology 2011; 132:410-420.
11. Xu Q, Pan X, Shu X, Cao H, Li X, Zhang K, et al. Increased interleukin-32 expression in chronic hepatitis B virus-infected liver. J Infect 2012; 65:336-342.
12. Rasool ST, Tang H, Wu J, Li W, Mukhtar MM, Zhang J, et al. Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication. Immunol Lett 2008; 117:161-167.
13. Pan X, Cao H, Lu J, Shu X, Xiong X, Hong X, et al. Interleukin-32 expression induced by hepatitis B virus protein X is mediated through activation of NF-kappaB. Mol Immunol 2011; 48:1573-1577.
14. Moschen AR, Fritz T, Clouston AD, Rebhan I, Bauhofer O, Barrie HD, et al. Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology 2011; 53:1819-1829.
15. Zhou Y, Zhu Y. Important role of the IL-32 inflammatory network in the host response against viral infection. Viruses 2015; 7:3116-3129.
16. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci U S A 1994; 91:12013-12017.
17. Ayoub SS, Wood EG, Hassan SU, Bolton C. Cyclooxygenase expression and prostaglandin levels in central nervous system tissues during the course of chronic relapsing experimental autoimmune encephalomyelitis (EAE). Inflamm Res 2011; 60:919-928.
18. Mohammadi A, Fazeli B, Taheri M, Sahebkar A, Poursina Z, Vakili V, et al. Modulatory effects of curcumin on apoptosis and cytotoxicity-related molecules in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Biomed Pharmacother 2017; 85:457-462.
19. Rezaee SAR, Editors. (Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)). Blood 2009; 113: 6528-6532.
20. Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, Jacobson S. Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load. JID 2001; 183:197-205.
21. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol 1998; 4:586-593.
22. Hong J, Bae S, Kang Y, Yoon D, Bai X, Chan ED, et al. Suppressing IL-32 in monocytes impairs the induction of the proinflammatory cytokines TNFalpha and IL-1beta. Cytokine 2010; 49:171-176.
23. Alsaleh G, Sparsa L, Chatelus E, Ehlinger M, Gottenberg JE, Wachsmann D, et al. Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther 2010; 12:R135.
24. Heinhuis B, Koenders MI, van de Loo FA, Netea MG, van den Berg WB, Joosten LA. Inflammation-dependent secretion and splicing of IL-32{gamma} in rheumatoid arthritis. Proc Natl Acad Sci U S A 2011; 108:4962-4967.
25. Netea MG, Azam T, Lewis EC, Joosten LA, Wang M, Langenberg D, et al. Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. PLoS Med 2006; 3:e277.
26. Bai X, Kim SH, Azam T, McGibney MT, Huang H, Dinarello CA, et al. IL-32 is a host protective cytokine against Mycobacterium tuberculosis in differentiated THP-1 human macrophages. J Immunol 2010; 184:3830-3840.
27. Lai KY, Chou YC, Lin JH, Liu Y, Lin KM, Doong SL, et al. Maintenance of epstein-barr virus latent status by a novel mechanism, latent membrane protein 1-induced interleukin-32, via the protein kinase cdelta pathway. J Virol 2015; 89:5968-5980.
28. Smith AJ, Toledo CM, Wietgrefe SW, Duan L, Schacker TW, Reilly CS, et al. The immunosuppressive role of IL-32 in lymphatic tissue during HIV-1 infection. J Immunol 2011; 186:6576-6584.
29. Nold MF, Nold-Petry CA, Pott GB, Zepp JA, Saavedra MT, Kim S-H, et al. Endogenous IL-32 controls cytokine and HIV-1 production. J Immunol 2008; 181:557-565.
30. Porrua O, Libri D. Transcription termination and the control of the transcriptome: why, where and how to stop. Nat Rev Mol Cell Biol 2015; 16:190-202.
31. Kang J-W, Park YS, Lee DH, Kim MS, Bak Y, Ham SY, et al. Interaction network mapping among IL-32 isoforms. Biochimie 2014; 101:248-251.
32. Bae S, Kang D, Hong J, Chung B, Choi J, Jhun H, et al. Characterizing antiviral mechanism of interleukin-32 and a circulating soluble isoform in viral infection. Cytokine 2012; 58:79-86.
33. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med 1999; 106:37S-42S.
34. Gandhi J, Khera L, Gaur N, Paul C, Kaul R. Role of modulator of inflammation cyclooxygenase-2 in gammaherpesvirus mediated tumorigenesis. Front Microbiol 2017; 8:538.
35. Steer SA, Corbett JA. The role and regulation of COX-2 during viral infection. Viral Immunol 2003; 16:447-460.
36. Li W, Liu Y, Mukhtar MM, Gong R, Pan Y, Rasool ST, et al. Activation of interleukin-32 pro-inflammatory pathway in response to influenza A virus infection. PLoS One 2008; 3:e1985.
37. Savard M, Bélanger C, Tremblay MJ, Dumais N, Flamand L, Borgeat P, et al. EBV suppresses prostaglandin E2 biosynthesis in human monocytes. J Immunol 2000; 164:6467-6473.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 7
July 2021
Pages 992-996

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