title: Renal TLR4 mRNA expression correlates with inflammatory marker MCP-1 and profibrotic molecule TGF-β₁ in patients with chronic kidney disease.
abstract: BACKGROUND
  Toll-like receptor-4 (TLR4) has been implicated in the pathogenesis of different renal diseases in rodent models. However, in human kidney disease, TLR4 expression and regulation is not well understood. We hypothesized that renal TLR4 expression plays a role in chronic kidney disease (CKD) and is associated with proteinuria, kidney function, histological diagnosis, and inflammatory mediators.
  
  
  METHODS
  We quantified TLR4 mRNA as well as expression of macrophage chemoattractant protein-1 (MCP-1), transforming growth factor-β₁ (TGF-β₁) and interleukin-6 (IL-6) in human kidney biopsies from 70 patients with CKD. We measured kidney function, urinary MCP-1 protein excretion, and the amount of chronic damage. Macrophage load was quantified by CD68 and vascularization by CD34 immunostaining.
  
  
  RESULTS
  TLR4 expression correlated significantly with MCP-1 and TGF-β₁ expression. High TLR4 expression was associated with high IL-6 expression. TLR4 expression was significantly upregulated in patients with severe proteinuria, and in patients with chronic ischemic renal damage and IgA nephropathy, when compared to patients with thin glomerular basement membrane disease. TLR4 expression did not correlate with creatinine clearance, renal outcome, macrophage load or chronic damage.
  
  
  CONCLUSIONS
  We show for the first time that renal TLR4 expression was significantly associated with the pro-inflammatory marker MCP-1 and the profibrotic molecule TGF-β₁ in kidney biopsies from patients with CKD, suggesting that increased expression of TLR4 is an important feature of CKD.
authors.affiliation: KfH Dialysis Center Bismarckstrasse, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Lepenies
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Eardley
authors.forename: Tina
authors.initials: T
authors.lastname: Kienitz
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
authors.forename: Thomas
authors.initials: T
authors.lastname: Ihl
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018932:Chemokine CCL2 / Q000032:analysis / Q000652:urine; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply*; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D018709:Statistics, Nonparametric; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007375:Interleukin-1; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D003404:Creatinine