Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages

Kota V. Ramana, Satish K. Srivastava

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Aldose reductase (AR; AKR1B1) a member of aldo-keto reductase super family, that we had shown earlier mediates cytotoxic signals induced by high glucose, cytokines and growth factors, also mediates the inflammatory signals induced by Gram-negative bacterial endotoxin, lipopolysaccharide (LPS). Inhibition of AR by three distinct AR inhibitors sorbinil, tolrestat or zopolrestat suppressed the LPS-induced production of inflammatory cytokines such as TNF-α, IL-6, IL-1β, IFN-γ, and chemokine MCP-1 in murine peritoneal macrophages. Inhibition of AR also prevented the production of nitric oxide, and prostaglandin E2 and expression of iNOS and Cox-2 proteins. The LPS-induced DNA binding activity of NF-κB and AP1 were significantly inhibited by AR inhibitors, and this effect was mediated through the inhibition of phosphorylation of IκB-α, IKK α/β and PKC. These results suggest the therapeutic use of AR inhibitors as anti-inflammatory drugs.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalCytokine
Volume36
Issue number3-4
DOIs
StatePublished - Nov 1 2006

Keywords

  • Aldose reductase
  • Inflammation
  • Lipopolysaccharide
  • NF-κB
  • Sepsis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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