Sulforaphane Suppresses LPS-induced Inflammation in Primary Rat Microglia

Inflamm Res. 2010 Jun;59(6):443-50. doi: 10.1007/s00011-009-0116-5. Epub 2009 Nov 19.

Abstract

Objective and design: The aim of this study was to investigate the signal transduction pathways involved in sulforaphane (SF) mediated inhibition of the inflammatory response to lipopolysaccharide (LPS). Additionally, we investigated the effects of SF and LPS on the activity of Nrf2.

Material: Primary rat microglia and the murine microglia cell line BV2 were used.

Treatment: Cells were treated with LPS with or without SF.

Methods: Cell viability was measured via WST-assay. Real-time RT-PCR was performed to analyze cytokine mRNA levels. The nitric oxide (NO) release was measured in LPS-stimulated microglia. The induction of various signal transduction pathways and Nrf2 was determined by Western blotting. NF-kappaB and AP-1 activation was measured by dual luciferase assay.

Results: We showed that SF attenuates the LPS-induced increase of IL-1beta, IL-6, and TNF-alpha expression in microglia. In addition, SF significantly decreases the NO in a concentration-dependent manner. SF inhibits LPS-stimulated ERK1/2 and JNK phosphorylation and thereby inhibits the LPS-induced activation of NF-kappaB- and activator protein-1 (AP-1). Moreover, SF and LPS together are able to induce Nrf2 activation.

Conclusions: We showed that SF, and also LPS by itself, are able to activate the cell's defence against oxidative and electrophilic stress. We conclude that SF could be a candidate agent for anti-inflammatory treatment of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents*
  • Blotting, Western
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Isothiocyanates
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / antagonists & inhibitors*
  • Luciferases / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • NF-E2-Related Factor 2 / biosynthesis
  • NF-E2-Related Factor 2 / genetics
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitrites / metabolism
  • Phosphorylation
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Thiocyanates / adverse effects
  • Thiocyanates / pharmacology*
  • Transcription Factor AP-1 / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Isothiocyanates
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Nitrites
  • RNA, Messenger
  • Thiocyanates
  • Transcription Factor AP-1
  • Luciferases
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • sulforafan