Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from children with Henoch-Schönlein purpura nephritis

Chang,Hong; Yu,Dong-Sheng; Liu,Xiu-Qin; Zhang,Qiu-Ye; Cheng,Na; Zhang,Shou-Qing; Qu,Zheng-Hai

doi:10.3892/etm.2014.1638

Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from children with Henoch-Schönlein purpura nephritis

Authors:
- Hong Chang
- Dong-Sheng Yu
- Xiu-Qin Liu
- Qiu-Ye Zhang
- Na Cheng
- Shou-Qing Zhang
- Zheng-Hai Qu
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Affiliations: Department of Pediatrics, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Department of Interventional Medicine, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Department of Pediatrics, Municipal Hospital of Qingdao, Qingdao, Shandong 266071, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/etm.2014.1638
Pages: 1703-1707

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Abstract

The aim of the present study was to investigate the expression levels and clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood mononuclear cells (PBMCs) collected from children with Henoch‑Schönlein purpura (HSP) nephritis. The randomized controlled trial was conducted between August 2011 and March 2013, and 105 children with a clinical diagnosis of HSP were enrolled in the study. According to the 24‑h urinary protein measurements and the presence of renal damage, the 105 cases were divided into groups A, B and C as follows: Group A, children with HSP but without renal damage; group B, children with HSP nephritis but without proteinuria; group C, children with HSP nephritis and proteinuria. A total of 30 healthy children were enrolled in the normal control group (group N). The primary endpoints were the detection of TLR3 and 4 mRNA and protein expression levels in PBMCs by flow cytometry and quantitative polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the PBMCs were significantly higher in groups A, B and C when compared with group N. In addition, the mRNA and protein expression levels of TLR4 in group C were much higher when compared with groups A and B. A positive correlation was identified between TLR4 protein expression and 24‑h urinary protein levels in group C. The expression levels of TLR3 did not significantly differ among the groups. Protein and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited a positive correlation with urinary protein excretion. These results indicate that aberrant activation of TLR4 may be relevant to the development of HSP nephritis.

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1	Jauhola O, Ronkainen J, Koskimies O, et al: Clinical course of extrarenal symptoms in Henoch-Schonlein purpura: a 6-month prospective study. Arch Dis Child. 95:871–876. 2010. View Article : Google Scholar : PubMed/NCBI
2	Punnoose AR, Lynm C and Golub RM: JAMA patient page. Henoch-Schönlein purpura. JAMA. 307:7422012.
3	Lau KK, Suzuki H, Novak J and Wyatt RJ: Pathogenesis of Henoch-Schönlein purpura nephritis. Pediatr Nephrol. 25:19–26. 2010.
4	Brown J, Wang H, Hajishengallis GN and Martin M: TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J Dent Res. 90:417–427. 2011. View Article : Google Scholar : PubMed/NCBI
5	Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A and Rysz J: The role of Toll-like receptors in renal diseases. Nat Rev Nephrol. 6:224–235. 2010. View Article : Google Scholar : PubMed/NCBI
6	Akil I, Ozkinay F, Onay H, Canda E, Gumuser G and Kavukcu S: Assessment of Toll-like receptor-4 gene polymorphism on pyelonephritis and renal scar. Int J Immunogenet. 39:303–307. 2012. View Article : Google Scholar : PubMed/NCBI
7	Eleftheriadis T, Pissas G, Liakopoulos V, Stefanidis I and Lawson BR: Toll-like receptors and their role in renal pathologies. Inflamm Allergy Drug Targets. 11:464–477. 2012. View Article : Google Scholar : PubMed/NCBI
8	Amura CR, Renner B, Lyubchenko T, Faubel S, Simonian PL and Thurman JM: Complement activation and toll-like receptor-2 signaling contribute to cytokine production after renal ischemia/reperfusion. Mol Immuno. 52:249–257. 2012. View Article : Google Scholar : PubMed/NCBI
9	Ozen S, Ruperto N, Dillon MJ, et al: EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 65:936–941. 2006. View Article : Google Scholar : PubMed/NCBI
10	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Method. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
11	Brown J, Wang H, Hajishengallis GN and Martin M: TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J Dent Res. 90:417–427. 2011. View Article : Google Scholar : PubMed/NCBI
12	Jin B, Sun T, Yu XH and Yeo AE: The effects of TLR activation on T-cell development and differentiation. Clin Dev Immunol. 2012:8364852012.PubMed/NCBI
13	Qian C and Cao X: Regulation of Toll-like receptor signaling pathways in innate immune responses. Ann NY Acad Sci. 1283:67–74. 2013. View Article : Google Scholar : PubMed/NCBI
14	Negishi H, Yanai H, Nakajima A, et al: Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol. 13:659–666. 2012. View Article : Google Scholar : PubMed/NCBI
15	Mills KH: TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol. 11:807–822. 2011.PubMed/NCBI
16	Urbonaviciute V, Starke C, Pirschel W, et al: Toll-like receptor 2 is required for autoantibody production and development of renal disease in pristane-induced lupus. Arthritis Rheum. 65:1612–1623. 2013. View Article : Google Scholar : PubMed/NCBI
17	Miranda-Hernandez S and Baxter AG: Role of toll-like receptors in multiple sclerosis. Am J Clin Exp Immunol. 2:75–93. 2013.PubMed/NCBI
18	Kirchner M, Sonnenschein A, Schoofs S, Schmidtke P, Umlauf VN and Mannhardt-Laakmann W: Surface expression and genotypes of Toll-like receptors 2 and 4 in patients with juvenile idiopathic arthritis and systemic lupus erythematosus. Pediatr Rheumatol Online J. 11:92013. View Article : Google Scholar : PubMed/NCBI
19	Brown HJ, Sacks SH and Robson MG: Toll-like receptor 2 agonists exacerbate accelerated nephrotoxic nephritis. J Am Soc Nephrol. 17:1931–1939. 2006. View Article : Google Scholar : PubMed/NCBI
20	Coppo R, Camilla R, Amore A, et al: Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy. Clin Exp Immunol. 159:73–81. 2010. View Article : Google Scholar : PubMed/NCBI
21	Pawar RD, Castrezana Lopez L, Allam R, et al: Bacterial lipopeptide triggers massive albuminuria in murine lupus nephritis by activating Toll-like receptor 2 at the glomerular filtration barrier. Immunology. 128(1 Suppl): e206–e221. 2009. View Article : Google Scholar
22	Lucas K and Maes M: Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 48:190–204. 2013. View Article : Google Scholar : PubMed/NCBI