title: Differential effects of advanced glycation end-products on renal tubular cell inflammation.
abstract: OBJECTIVE
  The authors recently showed that advanced glycation end-products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)-8 and soluble intercellular adhesion molecule-1 (sICAM-1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine-albumin may participate in diabetic tubular injury.
  
  
  METHODS
  Human proximal tubular epithelial cells (PTEC) were growth-arrested and exposed to methylglyoxal (MG), MG-bovine serum albumin (BSA)-AGE, carboxymethyllysine (CML)-BSA, AGE-BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro-inflammatory effect of GA alone.
  
  
  RESULTS
  MG-BSA-AGE and AGE-BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF), whereas CML-BSA stimulated expression of IL-6, CCL-2, CTGF, TGF-β and VEGF. These AGE compounds also activated nuclear factor (NF)-κB and their effects were attenuated by pre-incubation with anti-RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG-BSA-AGE, AGE-BSA or CML-BSA on PTEC.
  
  
  CONCLUSIONS
  AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF-κB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted.
authors.affiliation: Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. scwtang@hku.hk
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.forename: Loretta Y Y
authors.initials: LY
authors.lastname: Chan
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Amy S
authors.initials: AS
authors.lastname: Cheng
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Lan
authors.forename: Kar N
authors.initials: KN
authors.lastname: Lai
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011765:Pyruvaldehyde / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D000077154:Rosiglitazone; D012709:Serum Albumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000093423:Glycated Serum Albumin
chemical_list: D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; C526317:CCN2 protein, human; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012709:Serum Albumin; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C081628:advanced glycation end products-bovine serum albumin; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor; D012710:Serum Albumin, Bovine; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; D008239:Lysine; D000093423:Glycated Serum Albumin