Research Article


DOI :10.26650/experimed.2019.19020   IUP :10.26650/experimed.2019.19020    Full Text (PDF)

Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG)

Ceyda Nur BaltacıVuslat YılmazCanan Aysel UlusoyBurçak VuralErdem Tüzün

Objective: Despite the clues that myasthenia gravis (MG) disease may be associated with inflammasomes, there are no studies in the literature on MG disease and inflammasome complexes. Hence, to address this question, we investigated the possible participation of inflammasomes in experimental autoimmune myasthenia gravis mouse model (EAMG).


Material and Method: EAMG was induced in mouse using acetylcholine receptor (AChR) protein, and Anti-AChR IgG antibody levels detected by ELISA in the experimental group confirmed our model. Levels of CASP1, IL-1β, NLRP3, P2X7R, and AKT1 of the experimental and control (complete Freund’s adjuvant -CFA immunized) groups were measured by qRT-PCR.


Results: After immunization, the AChR IgG antibody levels were significantly higher in the AChR-immunized group than in the control group (p=0.042). IL-1β levels in the experimental group were significantly higher, compared to the control group (p=0.01). CASP1, NLRP3, and P2X7R levels were also higher compared to the control group. However, these differences did not attain statistical significance (p>0.05). AKT1 levels were lower compared to the control group. There was no correlation between serum antibody concentration and gene expression levels.


Conclusion: Our results suggest that there might be inflammasome involvement in the pathology of MG disease. Increase in IL-1β levels indicates the importance of the inflammatory response; however, further studies are necessary to confirm this. 

DOI :10.26650/experimed.2019.19020   IUP :10.26650/experimed.2019.19020    Full Text (PDF)

Deneysel Otoimmün Miyastenia Gravis Fare Modelinde İnflamazom Komplekslerinin Ekspresyon Seviyesi

Ceyda Nur BaltacıVuslat YılmazCanan Aysel UlusoyBurçak VuralErdem Tüzün

Amaç: Myastenia Gravis (MG) hastalığının inflamazomlarla ilişkili olabileceğine dair ipuçlarına rağmen literatürde MG hastalığı ve inflamazomlarla ilgili bir araştırma yer almamaktadır. Bu çalışmada, inflamazom kompleksinde yer alan genler ile hastalıktaki inflamatuvar yanıt arasındaki ilişkinin belirlenmesi hedeflenmiştir.


Gereç ve Yöntem: Deneysel otoimmün myastenia gravis (DOMG) modeli farelerde asetil kolin reseptör-(AChr) proteini kullanılarak oluşturuldu ve deney grubunda ELISA ile saptanan anti-AChR Ig seviyeleri modelimizi doğruladı. Deney ve kontrol (complete Freund’s adjuvant-CFA) immünize grubunda CASP1, IL-1β, NLRP3, P2X7R ve AKT1 gen ekspresyonu seviyeleri qRT-PCR ile incelendi.


Bulgular: İmmünizasyon sonrası AChR IgG antikor düzeyleri AChR-immünize grupta kontrollere göre anlamlı derecede yüksek belirlendi (p=0,042). Deney grubunda IL-1β seviyelerinin, kontrol grubuna kıyasla anlamlı derecede yüksek bulunmuştur (p=0,01). CASP1, IL-1β, NLRP3 ve P2X7R seviyelerinin de kontrol grubuna göre arttığı fakat istatistiksel anlamlılığa ulaşmadığı tespit edilmiştir (p>0,05). AKT1 seviyelerinin ise kontrol grubuna kıyasla azaldığı görülmüştür. Serum antikor düzeyleri ve gen ekspresyon seviyeleri arasında ise korelasyon saptanmamıştır.


Sonuç: Bulgularımız MG hastalığının patogenezinde inflamazom komplekslerinin rolü olabileceğini göstermiştir. IL-1β ekspresyon düzeyindeki anlamlı artış inflamasyon yanıtının önemine işaret etmektedir, fakat kesin bir kanıya varabilmek için bu konuda daha ileri çalışmalar yapılması gerektiği sonucuna ulaşmışıltır


PDF View

References

  • 1. Tüzün E, Yılmaz V, Parman Y, Oflazer P, Deymeer F, Saruhan-Direskeneli G. Increased complement consumption in MuSK-antibody-positive myasthenia gravis patients. Med Princ Pract 2011; 20: 581-3. [CrossRef] google scholar
  • 2. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol 2002; 2: 797-804. [CrossRef] google scholar
  • 3. Tüzün E, Scott BG, Goluszko E, Higgs S, Christadoss P. Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis. J Immunol; 171: 3847-54. [CrossRef] google scholar
  • 4. Sahashi K, Engel AG, Linstrom JM, Lambert EH, Lennon VA. Ultrastructural localization of immune complexes (IgG and C3) at the end-plate in experimental autoimmune myasthenia gravis. J Neuropathol Exp Neurol 1978; 37: 212-23. [CrossRef] google scholar
  • 5. Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin Invest 2006; 116: 2843-54. [CrossRef] google scholar
  • 6. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 2015; 21: 677-87. [CrossRef] google scholar
  • 7. Christadoss P, Poussin M, Deng C. Animal models of myasthenia gravis. Clin Immunol 2000; 95: 75-87. [CrossRef] google scholar
  • 8. Zhang JM, An J. Cytokines, inflammation and pain. Int Anesthesiol Clin 2007; 45: 27-37. [CrossRef] google scholar
  • 9. Wang CC, Li H, Zhang M, Li XL, Yue LT, Zhang P, et al. Caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate dendric cell IL-1-IL-17 pathway. J Neuroinflammation 2015; 10.1186/s12974-015-0334-4. [CrossRef] google scholar
  • 10. Fan Z, Söder S, Oehler S, Fundel K, Aigner T. Activation of Interleukin-1 signaling cascades in normal and osteoarthritic articular cartilage. Am J Pathol 2007; 171: 938-46. [CrossRef] google scholar
  • 11. Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 2013; 12: doi: 10.1186/1476-4598-12-86. [CrossRef] google scholar
  • 12. Zhang Y, Zhang Y, Li H, Jia X, Zhang X, Xia Y, et al. Increased expression of P2X7 receptor in peripheral blood mononuclear cells correlates with clinical severity and serum levels of Th17-related cytokines in patients with myasthenia gravis. Clin Neurol Neurosurg 2017; 157: 88-94. [CrossRef] google scholar
  • 13. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 2001; 3: 1014-9. [CrossRef] google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Baltacı, C., Yılmaz, V., Ulusoy, C.A., Vural, B., & Tüzün, E. (2019). Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG). Experimed, 9(3), 79-85. https://doi.org/10.26650/experimed.2019.19020


AMA

Baltacı C, Yılmaz V, Ulusoy C A, Vural B, Tüzün E. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG). Experimed. 2019;9(3):79-85. https://doi.org/10.26650/experimed.2019.19020


ABNT

Baltacı, C.; Yılmaz, V.; Ulusoy, C.A.; Vural, B.; Tüzün, E. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG). Experimed, [Publisher Location], v. 9, n. 3, p. 79-85, 2019.


Chicago: Author-Date Style

Baltacı, Ceyda Nur, and Vuslat Yılmaz and Canan Aysel Ulusoy and Burçak Vural and Erdem Tüzün. 2019. “Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG).” Experimed 9, no. 3: 79-85. https://doi.org/10.26650/experimed.2019.19020


Chicago: Humanities Style

Baltacı, Ceyda Nur, and Vuslat Yılmaz and Canan Aysel Ulusoy and Burçak Vural and Erdem Tüzün. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG).” Experimed 9, no. 3 (Apr. 2024): 79-85. https://doi.org/10.26650/experimed.2019.19020


Harvard: Australian Style

Baltacı, C & Yılmaz, V & Ulusoy, CA & Vural, B & Tüzün, E 2019, 'Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG)', Experimed, vol. 9, no. 3, pp. 79-85, viewed 20 Apr. 2024, https://doi.org/10.26650/experimed.2019.19020


Harvard: Author-Date Style

Baltacı, C. and Yılmaz, V. and Ulusoy, C.A. and Vural, B. and Tüzün, E. (2019) ‘Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG)’, Experimed, 9(3), pp. 79-85. https://doi.org/10.26650/experimed.2019.19020 (20 Apr. 2024).


MLA

Baltacı, Ceyda Nur, and Vuslat Yılmaz and Canan Aysel Ulusoy and Burçak Vural and Erdem Tüzün. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG).” Experimed, vol. 9, no. 3, 2019, pp. 79-85. [Database Container], https://doi.org/10.26650/experimed.2019.19020


Vancouver

Baltacı C, Yılmaz V, Ulusoy CA, Vural B, Tüzün E. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG). Experimed [Internet]. 20 Apr. 2024 [cited 20 Apr. 2024];9(3):79-85. Available from: https://doi.org/10.26650/experimed.2019.19020 doi: 10.26650/experimed.2019.19020


ISNAD

Baltacı, Ceyda Nur - Yılmaz, Vuslat - Ulusoy, CananAysel - Vural, Burçak - Tüzün, Erdem. Expression Levels of Inflammasome Complexes in Experimental Autoimmune Myasthenia Gravis Mouse Model (EAMG)”. Experimed 9/3 (Apr. 2024): 79-85. https://doi.org/10.26650/experimed.2019.19020



TIMELINE


Last Revision09.10.2019
Accepted25.10.2019

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.