Guggulsterone Attenuated Lipopolysaccharide-Induced Inflammatory Responses in Mouse Inner Medullary Collecting Duct-3 Cells

Inflammation. 2016 Feb;39(1):87-95. doi: 10.1007/s10753-015-0226-x.

Abstract

Guggulsterone (GS) is a phytosterol that has been used to treat inflammatory diseases such as colitis, obesity, and thrombosis. Although many previous studies have examined activities of GS, the effect of GS on lipopolysaccharide (LPS)-induced inflammatory responses in mouse inner medullary collecting duct-3 (mIMCD-3) cells have not been examined. Therefore, here, we investigated the anti-inflammatory action of GS on mIMCD-3 cells exposed to LPS. LPS treatment on mIMCD-3 cells produced pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) significantly; however, GS treatment significantly inhibited the production of pro-inflammatory molecules. In addition, GS inhibited the degradation of Iκ-Bα and translocation of NF-κB on mIMCD-3 cells. These results suggest that GS could inhibit inflammatory responses in collecting duct cells which could contribute to kidney injury during systemic infection.

Keywords: guggulsterone (GS); inflammation; inner medullary collecting duct (IMCD); lipopolysaccharide (LPS); toll-like receptor 4 (TLR4).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / biosynthesis
  • Female
  • Inflammation / drug therapy
  • Interleukin-6 / biosynthesis
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / immunology*
  • Lipopolysaccharides
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha / metabolism
  • Nitric Oxide Synthase Type II / biosynthesis
  • Pregnenediones / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4 / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • Lipopolysaccharides
  • Pregnenediones
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • pregna-4,17-diene-3,16-dione
  • Nitric Oxide Synthase Type II
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2