title: Renal expression of Toll-like receptor 2 and 4: dynamics in human allograft injury and comparison to rodents.
abstract: Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated pre- and post-transplantation protein expression of TLR2 and TLR4 in human kidney biopsies. Human kidney biopsies obtained from living kidney donors and patients with acute tubular necrosis, acute cellular and vascular rejection and interstitial fibrosis/tubular atrophy (IF/TA) were used. Translating results from animal studies to the clinical situation is highly important considering the upcoming clinical studies with TLR inhibitors in human renal transplantation. Hence, the TLR2 and TLR4 expression in healthy mouse and rat kidneys was analyzed and compared with human kidneys. In healthy human kidneys, TLR2 is expressed on the endothelium and Bowman's capsule, while TLR4 is expressed on the endothelium only. No tubular staining was found for both receptors in human kidneys. In contrast to human biopsies, TLR2 and TLR4 expression in rodents was observed on tubular epithelial cells. In all acute rejection human biopsies, increased infiltration of TLR4(+) leukocytes was observed. In conclusion, a discrepancy exists between human and rodent renal TLR expression, which suggests careful attention when translating results from rodent studies to the human situation. Additionally, this study revealed human TLR2 and TLR4 expression dynamics in human biopsies pre- and post-transplantation.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: e.g.d.stribos@umcg.nl.
authors.forename: Elisabeth G D
authors.initials: EG
authors.lastname: Stribos
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Maaike B
authors.initials: MB
authors.lastname: van Werkhoven
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Felix
authors.initials: F
authors.lastname: Poppelaars
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen Research Institute of Pharmacy, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Olinga
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.affiliation: Department of Pathology, University of Amsterdam, Academic Medical Center, The Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Damman
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Seelen
mesh_terms: D000328:Adult; D064591:Allografts / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000918:Antibody Specificity; D001706:Biopsy; D003710:Demography; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D051379:Mice; D008875:Middle Aged; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Inflammation; Kidney; Toll-like receptor 2; Toll-like receptor 4; Transplantation