TLR4-mediated Neuroinflammation in SLE through phosphorylation of MyD88/IRAK signaling pathway

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Research Article
American Journal of BioMedicine Volume 3, Issue 9, pages 581-596
Published: September 29, 2015

Gang Li, Wu Zhao,Tracey B Finn, Wilma Martin, Chris J Leung

A role for innate immunity in inflammation of CNS is being increasingly evidenced. This study focused on determining the role of toll-like receptor 4 (TLR4) and phosphorylation of MyD88/IRAK signaling pathway in systemic lupus erythematosus (SLE) pathogenesis. We used mouse models of SLE (BXSB/Yaa mice) and their controls (C57BL/6 mice). TLR4 significantly phosphorylation of MyD88/IRAK activity and enhanced SLE pathogenesis in BXSB/Yaa mice, whereas the small interference RNA-mediated knockdown of TLR4 activity attenuated SLE activity.

Keywords: TLR4; SLE; MyD88; IRAK



1. Murphy K, Innate Immunity: The First Lines of Defense. Janeway's Immunobiology, Garland Science, Taylor & Francis Group, Abingdon, UK, 8th edition, 2012.

2. Aran AA, Putterman C. Treatment of lupus nephritis: facing the era of immunotherapy. Panminerva Med 2008; 50:235–245. [PubMed]

2. Nimmerjahn A, Kirchhoff F, Helmchen F. Neuroscience: resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005;308:1314–1318. [Abstract/Full-Text]

3. Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. Journal of Clinical Pathology 2003;56(7):481–490. [PubMed]

4. Pisetsky DS. Systemic lupus erythematosus. A. Epidemiology, pathology and pathogenesis. In: Klippel JH, ed. Primer on the rheumatic diseases, 11th ed. Georgia, USA: Arthritis Foundation, 1997:246–51.

5. Yun HR, Koh HK, Kim SS, et al. FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients. Lupus 2001;10:466–72. [PubMed]

6. Kim F, Pham M, Luttrell I, et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circulation Research 2007;100(11):1589–1596. [Abstract/Full-Text]

7. Gangloff M. Different dimerisation mode for TLR4 upon endosomal acidification? Trends Biochem. Sci 2012; 37:92–98. [PubMed]

8. Shi H, Kokoeva MV, Inouye K, et al. TLR-4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation 2006;116(11):3015–3025. [Abstract/Full-Text]

9. de Batista PR, Palacios R, Martín A, et al. TLR-4 upregulation by angiotensin II contributes to hypertension and vascular dysfunction through reactive oxygen species production. PLoS ONE 2014;9(8): e104020. [Abstract/Full-Text]

10. Wolf G, Bohlender J, Bondeva T, et al. Angiotensin II upregulates TLR-4 on mesangial cells. J Am Soc Nephrol 2006;17:1585–1593. [PubMed]

11. Sollinger D, Eißler R, Lorenz R, et al. Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in l-NAME-induced hypertension. Cardiovascular Research 2014;101(3):464–472. [Abstract/Full-Text]

12. Suganami T, Tanimoto-Koyama K, Nishida J, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 2007;27:84-91. [Abstract/Full-Text]

13. Bomfim GF, Dos Santos RA, Oliveira MA, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci (Lond) 2012;122:535-543. [Abstract/Full-Text]

14. Asehnoune K, Strassheim D, Mitra S, Kim JY, Abraham E. Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-κB. J Immunol 2004;172: 2522–2529. [PubMed]

15. Pi Y, Zhang LL, Li BH, et al. Inhibition of reactive oxygen species generation attenuates TLR4-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells. Lab Invest 2003;93: 880–887. [PubMed]

16. Zhang Z, Li W, Sun D, et al. TLR-4 signaling in dysfunction of cardiac microvascular endothelial cells under hypoxia/reoxygenation. Inflamm Res 2011;60: 37–45. [PubMed]

17. Liang CF, Liu JT, Wang Y, Xu A, Vanhoutte PM. TLR-4 mutation protects obese mice against endothelial dysfunction by decreasing NADPH Oxidase isoforms 1 and 4. Arterioscler Thromb Vasc Biol 2013; 33:777–784. [PubMed]

18. Marketou ME, Kontaraki JE, Zacharis EA, et al. TLR2 and TLR-4 gene expression in peripheral monocytes in nondiabetic hypertensive patients: the effect of intensive blood pressure-lowering. J Clin Hypertens (Greenwich) 2012;14: 330–335. [PubMed]

19. Sollinger D, Eiβler R, Lorenz S, et al. Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension. Cardiovasc Res 2014;101:464–472. [PubMed]

20. Bomfim GF, Dos Santos RA, Oliveira MA, et al. TLR-4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci  2012;122:535–543. [PubMed]

21. Eiβler R, Schmaderer C, Rusai K, et al. Hypertension augments cardiac TLR-4 expression and activity. Hypertens Res 2001;34:551–558. [PubMed]

22. Pineda A, Verdin-Terán SL, Camacho A, Moreno-Fierros L. Expression of Toll-like Receptor TLR-2, TLR-3, TLR-4 and TLR-9 is increased in placentas from patients with preeclampsia. Arch Med Res 2011;42:382–391. [PubMed]

23. Kim YM, Romero R, Oh SY, et al. TLR-4: a potential link between “danger signals,” the innate immune system, and preeclampsia? Am J Obstet Gynecol 2005;193:921–927. [PubMed]

24. Devaraj S, Dasu MR, Rockwood J, et al. Increased Toll-like Receptor (TLR) 2 and TLR-4 expression in monocytes from patients with Type 1 Diabetes: further evidence of a proinflammatory state. J Clin Endocrinol Metab 2008;93:578–583. [PubMed]

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