title: Glomerular cytokine expression in murine lupus nephritis.
abstract: BACKGROUND
  Aberrant expression of T helper cell (Th) cytokines is believed to play a central role in the pathogenesis of systemic lupus erythematosus (SLE). While the glomerulus is one of the major targets of lupus inflammation, little is known about the cytokine expression in glomeruli. The current study aimed to explore the profiles of Th cytokine gene expressions in isolated glomeruli of lupus-prone mice.
  
  
  METHODS
  Glomeruli were purified from lupus-prone MRL/lpr mice using the magnetic microbead method. Expressions of cytokine genes representing the Th subset and FoxP3 were examined using real-time polymerase chain reaction. Serum levels of these cytokines were also measured by enzyme-linked immunosorbent assay. MRL/n mice were used as controls. Histologic glomerular damages were scored semiquantitatively. To examine the role of TNF-α in glomerular damage, we administered etanercept, a TNF-α antagonist, into the subjects.
  
  
  RESULTS
  Glomerular gene expressions of TNF-α in lpr mice increased with week postpartum and reached statistically significant levels at 16 weeks compared with those of the glomeruli from control mice. Expressions of IFN-γ, IL-4 and FoxP3 also increased, but the difference was not significant. There was a significant increase in serum levels of TNF-α, IFN-γ, and IL-17 and decrease in those of IL-4. Among the genes examined, TNF-α significantly correlated with glomerular damage score. Administration of etanercept did not affect glomerular cytokine expressions or proteinuria and failed to ameliorate histologic glomerular damages.
  
  
  CONCLUSIONS
  Our data suggest that Th1 cytokines, especially TNF-α, are dominantly expressed in the glomeruli of lupus-prone mice, but its pathophysiological role remains unclear.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kadiombo Anastasie
authors.initials: KA
authors.lastname: Tshilela
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan. hikeuchi@gunma-u.ac.jp.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.affiliation: Dialysis and Rheumatology Center, Toho Hospital, 1155 Kasagake, Midori, Gunma, 379-2311, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Gunma Rheumatism Clinic, 1040 Ino, Takasaki, Gunma, 370-0004, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuroiwa
authors.affiliation: Dialysis and Rheumatology Center, Toho Hospital, 1155 Kasagake, Midori, Gunma, 379-2311, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakurai
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D000068800:Etanercept / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019463:Mice, Inbred MRL lpr; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001688:Biological Products; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000068800:Etanercept
keywords: Kidney glomerulus; Lupus nephritis; Th1–Th2 balance; Tumor necrosis factor-alpha