title: TNFα up-regulates COX-2 in chronic progressive nephropathy through nuclear accumulation of RelB and NF-κB2.
abstract: OBJECTIVE
  The pathogenesis of progressive nephropathies involves inflammatory factors. The inhibition of cyclooxygenase-2 (COX-2) can limit renal damage and inflammation. However, the mechanism of up-regulation of COX-2 in nephropathy is poorly defined.
  
  
  METHODS
  Here we found that tumor necrosis factor alpha (TNFα) was involved in expression of COX-2 in normal rat kidney (NRK) cell line.
  
  
  RESULTS
  TNFα stimulated COX-2 production in a time-dependent manner in NRK cells by inducing nuclear accumulation of RelB and nuclear factor kappa B2 (NF-κB2) and their association with COX-2 gene promoter. Depletion of IκB-inducing kinase alpha, a positive regulator of activation of p100 processing to active p52, attenuated TNFα-induced COX-2 production. Furthermore, TNFα induced COX-2 production and nuclear import in anti-thymocyte serum (ATS) nephropathy.
  
  
  CONCLUSIONS
  These data suggest that TNFα-RelB/p52 pathway may be involved in the early stages of renal damage, in part by stimulating COX-2 and inflammatory responses.
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Junsi
authors.initials: J
authors.lastname: Qiu
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Yuan
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Shujue
authors.initials: S
authors.lastname: Chen
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
authors.forename: Rongquan
authors.initials: R
authors.lastname: Chen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D051550:I-kappa B Kinase / Q000172:deficiency / Q000235:genetics; D008297:Male; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D052003:NF-kappa B p52 Subunit; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase
keywords: TNFα; TNFα-RelB/p52 pathway; anti-thymocyte serum nephropathy; cyclooxygenase-2; inflammatory; renal damage