Activation of NLRP1 and NLRP3 Inflammasomes in Multiple Sclerosis and Clinically Isolated Syndrome

Year 2021, Volume: 11 Issue: 4, 674 - 678, 26.10.2021

Tuba Tanyel , Özlem Mercan , Cemile Mısırlı Recai Türkoğlu

https://doi.org/10.33808/clinexphealthsci.730473

Abstract

Objective: Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease characterized with demyelination and axonal damage in central nervous system (CNS). Inflamasomes, which are important part of this inflammatory process, regulate maturation of proinflammatory cytokines. Infamazom complexes are thought to increase in MS attacks. We investigated role of inflammasome complexes (nod-like receptor protein 1 and 3) in serum and cerebrospinal fluid (CSF) levels for MS development.
Methods: Eighteen clinically isolated syndrome (CIS), 19 relapsing remitting multiple sclerosis (RRMS) and 20 healthy control cases were included in the study. Nod-like receptor protein 1 and 3 (NLRP1, NLRP3), inflammasome complex levels and oligoclonal band (OCB) patterns of all the groups were measured in serum and CSF samples using Enzyme-Linked Immuno Sorbent Assay (ELISA) method.
Results: Although NLRP1 and NLRP3 levels in both RRMS and CIS patients measured in serum and CSF were significantly higher than healthy control group, there was no statistically significant difference between RRMS and CIS patients. On the other hand, the levels of NLRP1 and NLRP3 in CSF were significantly higher in OCB pattern positive patients compared to the OCB pattern negative patients.
Conclusion: In this pilot study, it is shown that NLRP1 and NLRP3 inflammasome complexes increased in CSF samples of MS cases and that this tendency occurred during or maybe before the first MS attack. As a result, it was thought that these complexes may have an effect on the formation of the OCB band.

Keywords

multiple sclerosis, inflammasome complexes, clinical isolated synrome

References

• 1. Bar-Or A. Immunology of multiple sclerosis. Neurologic clinics. 2005;23(1):149-75.
• 2. Vidal-Jordana A, Montalban X. Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects. Neuroimaging Clinics of North America. 2017;27(2):195-204. doi: http://doi.org/10.1016/j.nic.2016.12.001.
• 3. Mukherji SK. Imaging in Multiple Sclerosis: Diagnosis and Management. Neuroimaging Clinics of North America. 2017;27(2):xv. doi: http://doi.org/10.1016/j.nic.2017.02.002.
• 4. Filippi M, Preziosa P, Rocca MA. Chapter 20 - Multiple sclerosis. In: Joseph CM, González RG, editors. Handbook of Clinical Neurology. Volume 135: Elsevier; 2016. p. 399-423.
• 5. Weinshenker BG, editor The natural history of multiple sclerosis: update 1998. Seminars in neurology; 1998: © 1998 by Thieme Medical Publishers, Inc.
• 6. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-32.
• 7. Rathinam VA, Vanaja SK, Fitzgerald KA. Regulation of inflammasome signaling. Nature immunology. 2012;13(4):333-42. 8. Khare S, Luc N, Dorfleutner A, Stehlik C. Inflammasomes and their activation. Critical Reviews™ in Immunology. 2010;30(5).
• 9. Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, Chen VS, Gris D, Matsushima GK, Ting JP-Y. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. Journal of Neuroscience. 2010;30(47):15811-20.
• 10. Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, Huang M, Schneider M, Miller SD, Ting JP-Y. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. The Journal of Immunology. 2010;185(2):974-81.
• 11. Shaw PJ, McDermott MF, Kanneganti T-D. Inflammasomes and autoimmunity. Trends in molecular medicine. 2011;17(2):57-64.
• 12. Freeman LC, Ting JPY. The pathogenic role of the inflammasome in neurodegenerative diseases. Journal of neurochemistry. 2016;136:29-38.
• 13. Barclay W, Shinohara ML. Inflammasome activation in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Brain Pathology. 2017;27(2):213-9.
• 14. Yang C-A, Chiang B-L. Inflammasomes and human autoimmunity: a comprehensive review. Journal of autoimmunity. 2015;61:1-8.
• 15. von Büdingen H-C, Gulati M, Kuenzle S, Fischer K, Rupprecht TA, Goebels N. Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce “oligoclonal bands”. Journal of neuroimmunology. 2010;218(1):134-9.
• 16. Nyúl-Tóth Á, Kozma M, Nagyőszi P, Nagy K, Fazakas C, Haskó J, Molnár K, Farkas AE, Végh AG, Váró G. Expression of pattern recognition receptors and activation of the non-canonical inflammasome pathway in brain pericytes. Brain, Behavior, and Immunity. 2017.
• 17. Noroozi S, Meimand HAE, Arababadi MK, Nakhaee N, Asadikaram G. The effects of IFN-β 1a on the expression of inflammasomes and apoptosis-associated speck-like proteins in multiple sclerosis patients. Molecular neurobiology. 2017;54(4):3031-7.
• 18. Farina G, Magliozzi R, Pitteri M, Reynolds R, Rossi S, Gajofatto A, Benedetti MD, Facchiano F, Monaco S, Calabrese M. Increased cortical lesion load and intrathecal inflammation is associated with oligoclonal bands in multiple sclerosis patients: a combined CSF and MRI study. Journal of neuroinflammation. 2017;14(1):40.