Novel nuclear factor κB activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction

Akira Miyajima, Takeo Kosaka, Kaori Seta, Tomohiko Asano, Kazuo Umezawa, Masamichi Hayakawa

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Purpose: We determined whether the novel nuclear factor κB activation inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which is derived from epoxyquinomicin C, affects renal inflammatory responses in unilateral ureteral obstruction. Materials and Methods: DHMEQ (8 mg./kg.) was administered to rats 1 day after unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 7 after unilateral ureteral obstruction. Tissue nuclear factor κB activity and transforming growth factor-β were determined by electrophoretic mobility shift assay and bioassay using mink lung epithelial cells, respectively. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cellular nuclear antigen and the TUNEL (Intergen, Purchase, New York) assay, respectively. Leukocyte infiltration was detected by immunostaining for CD45. Fibrosis was assessed by measuring tissue hydroxyproline content. Results: Unilateral ureteral obstruction for 7 days significantly activated nuclear factor κB, induced tubular apoptosis, proliferation and interstitial fibrosis in the obstructed kidney of the control group compared with their unobstructed counterparts (30.3 ± 4.5 nuclei per high power field versus 1.7 ± 0.4, 25.7 ± 3.3 nuclei per high power field versus 3.2 ± 0.4 and 6.2 ± 0.3 μmol. hydroxyproline per gm. tissue versus 3.4 ± 0.1, respectively). Conversely daily administration of DHMEQ (8 mg./kg.) significantly inhibited nuclear factor κB activation and decreased mean tubular apoptosis (9.5 ± 2.1 nuclei per high power field), proliferation (10.2 ± 2.4 nuclei per high power field) and interstitial fibrosis (4.9 ± 0.4 μmol. hydroxyproline per gm. tissue) in the obstructed kidney. Conclusions: Specific inhibition of nuclear factor κB can prevent inflammatory renal responses, suggesting that targeting nuclear factor κB activation may be feasible for preventing inflammatory kidney diseases.

Original languageEnglish
Pages (from-to)1559-1563
Number of pages5
JournalJournal of Urology
Volume169
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1
Externally publishedYes

Fingerprint

Ureteral Obstruction
Kidney
Hydroxyproline
Wounds and Injuries
Fibrosis
Apoptosis
Mink
Nuclear Antigens
In Situ Nick-End Labeling
Kidney Diseases
Thromboplastin
Transforming Growth Factors
Electrophoretic Mobility Shift Assay
Biological Assay
Leukocytes
Epithelial Cells
Lung
Control Groups
dehydroxymethylepoxyquinomicin

Keywords

  • Apoptosis
  • Inflammation
  • Kidney
  • Transcription factors
  • Ureteral obstruction

ASJC Scopus subject areas

  • Urology

Cite this

Novel nuclear factor κB activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction. / Miyajima, Akira; Kosaka, Takeo; Seta, Kaori; Asano, Tomohiko; Umezawa, Kazuo; Hayakawa, Masamichi.

In: Journal of Urology, Vol. 169, No. 4, 01.04.2003, p. 1559-1563.

Research output: Contribution to journalArticle

Miyajima, Akira ; Kosaka, Takeo ; Seta, Kaori ; Asano, Tomohiko ; Umezawa, Kazuo ; Hayakawa, Masamichi. / Novel nuclear factor κB activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction. In: Journal of Urology. 2003 ; Vol. 169, No. 4. pp. 1559-1563.
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AU - Miyajima, Akira

AU - Kosaka, Takeo

AU - Seta, Kaori

AU - Asano, Tomohiko

AU - Umezawa, Kazuo

AU - Hayakawa, Masamichi

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KW - Apoptosis

KW - Inflammation

KW - Kidney

KW - Transcription factors

KW - Ureteral obstruction

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