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- Title
Expression of Toll-Like Receptor 3 on Human Mesangial Cells and Its Role for Inflammatory Kidney Disease.
- Authors
Wörnle, M.; Banas, B.; Schmid, H.; Merkle, M.; Kretzler, M.; Gröne, H. -J.; Schlöndorff, D.
- Abstract
Objective: The immune system comprises innate and acquired immunity. Toll-like receptors (TLRs) are an essential part of the innate immune system for early recognition of pathogen-associated molecular patterns as well as receptors for endogenous 'danger signals'. We hypothesized that Toll-like receptors are important for the clearance of viral RNA accumulated in the glomerulus in a 'house-keeping' manner and play a role in the pathogenesis of glomerular deposits of viral RNA in combination with RNA-antibodies during inflammatory processes. Therefore, the expression of Toll-like receptors in the glomerulus and their role for inflammatory kidney diseases was investigated. Methods: ELISA and RT-PCR were performed in cell culture of human mesangial cells, immunohistochemistry of biopsies of healthy kidneys and RT-PCR of microdissected glomeruli of kidney biopsies were done. Results: We showed a basal expression of TLR3 on human mesangial cells in cell culture by RT-PCR. After stimulation with a combination of proinflammatory cytokines ((IL1-β, IFN-γ, TNF-α) the expression of TLR3 was increased. FACS analysis for TLR3 revealed a signal on the surface and after permeabilisation of the cells. After stimulation with poly (I:C), a synthetic analogon of viral RNA, we could observe an increased synthesis of RANTES/CCL21, measured by ELISA and RT-PCR, further increased by pretreatment of the cells with proinflammatory cytokines. Immunohistochemistry showed an expression of TLR3 in the glomerulus of normal human kidneys in a mesangial pattern. Analysis of kidney biopsies of patients with Ig-A nephritis by RT-PCR showed an increased expression of TLR3 as well as a coexpression of RANTES/CCL21 compared to healthy kidney donors. Conclusions: Our study implicates an association between the danger-receptor TLR3 for viral RNA expressed on human mesangial cells and its significance for inflammatory processes in the glomerulus. The expression and function of TLR3 in the glomerulus is of clinical interest for the pathogenesis of immunocomplex glomerulonephritis as well as for the progression of chronic glomerulonephritis.
- Subjects
IMMUNE system; RNA; IMMUNITY; PATHOGENIC microorganisms; VIRUSES
- Publication
Kidney & Blood Pressure Research, 2004, Vol 27, Issue 5/6, p297
- ISSN
1420-4096
- Publication type
Article