TLR3-dependent immune regulatory functions of human mesangial cells

Merkle, Monika; Ribeiro, Andrea; Köppel, Simone; Pircher, Joachim; Mannell, Hanna; Roeder, Maximilian von; Wörnle, Markus

doi:10.1038/cmi.2012.3

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…In numerous studies on IgAN pathogenesis, various types of receptors that could influence the development of this disease have been analyzed. These receptors were TLR3, mainly recognizing viral dsDNA [103]; TLR7 receptor [104]; binding to ssRNA viruses and TLR4 [105,106]; and binding of a variety of ligands, including LPS Gram-negative bacteria and DAMP (Table 2). Numerous observations of patients with diagnosed IgAN suggest the involvement of pathogens of viral origin, which is also confirmed by experimental models.…”

Section: Iga Nephropathy (Igan)mentioning

confidence: 99%

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Mertowski

Lipa

Morawska

et al. 2020

IJMS

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One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.

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Section: Iga Nephropathy (Igan)mentioning

confidence: 99%

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Mertowski

Lipa

Morawska

et al. 2020

IJMS

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“…One possible mechanism of TLR3 involved in the pathogenesis of CKD including lupus nephritis and chronic inflammatory renal disease may be due to its role in triggering the glomerular mesangial cells to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury [39][40][41][42] .…”

Section: Discussionmentioning

confidence: 99%

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.

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“…At cellular levels, the activation of TLR3 leads to increase pro-inflammatory substances including cytokines in mesangial cells [43,49,33,32,2]. Moreover, it has been demonstrated that its activation in podocytes leads to proteinuria.…”

Section: Discussionmentioning

confidence: 97%

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

Hardigan

Spitler

Matsumoto³

et al. 2015

Pflugers Arch - Eur J Physiol

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Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

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TLR3-dependent immune regulatory functions of human mesangial cells

Cited by 10 publications

References 32 publications

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway

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