The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury

Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The...

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Vydáno v:	PloS one Ročník 4; číslo 5; s. e5704
Hlavní autoři:	Leemans, Jaklien C., Butter, Loes M., Pulskens, Wilco P. C., Teske, Gwendoline J. D., Claessen, Nike, van der Poll, Tom, Florquin, Sandrine
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 27.05.2009 Public Library of Science (PLoS)
Témata:	Animals Apoptosis Biopsy Bone marrow Cell Proliferation Chemokines Chemokines - metabolism Chromosomal proteins Disease Progression Enzyme Activation Extracellular Matrix - metabolism Fibroblasts Fibroblasts - enzymology Fibroblasts - pathology Fibrosis Gene expression Glycoprotein gp96 Hazards HMGB1 protein Humans Hypotheses Immunology/Innate Immunity Inflammation Inflammation - immunology Inflammation - pathology Injuries Kidney - enzymology Kidney - pathology Kidney diseases Kidney Diseases - enzymology Kidney Diseases - immunology Kidney Diseases - pathology Kidney transplantation Kidney Tubules - metabolism Kidney Tubules - pathology Kidneys Leukocytes (neutrophilic) Ligands Localization Male Matrix Metalloproteinases - metabolism Mice Mice, Inbred C57BL Nephrology/Chronic Kidney Disease Nephrology/Tubulointerstitial Diseases Nephropathy Pathology Pathology/Immunology Physiological aspects Renal function Rodents TLR2 protein Toll-Like Receptor 2 - deficiency Toll-Like Receptor 2 - metabolism Toll-like receptors Transforming Growth Factor beta - metabolism Transforming growth factors Up-Regulation Ureteral Obstruction - enzymology Ureteral Obstruction - pathology
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/-) or TLR2(+/+) mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/-) mice compared with TLR2(+/+) animals. Although, the obstructed kidneys of TLR2(-/-) mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: JCL LB WP GT NC TvdP SF. Performed the experiments: JCL LB WP GT NC. Analyzed the data: JCL LB WP GT NC TvdP SF. Contributed reagents/materials/analysis tools: TvdP. Wrote the paper: JCL SF.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0005704