Stimulation of phagocytosis by sulforaphane

Biochem Biophys Res Commun. 2011 Feb 4;405(1):146-51. doi: 10.1016/j.bbrc.2011.01.025. Epub 2011 Jan 8.

Abstract

Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2(-/-) mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Line
  • Culture Media / chemistry
  • Cytoskeletal Proteins / metabolism
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Intramolecular Oxidoreductases / metabolism
  • Isothiocyanates
  • Kelch-Like ECH-Associated Protein 1
  • Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Macrophages, Peritoneal / drug effects*
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Phagocytosis / drug effects*
  • Phagocytosis / genetics
  • Thiocyanates / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Culture Media
  • Cytoskeletal Proteins
  • Isothiocyanates
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • Macrophage Migration-Inhibitory Factors
  • NF-E2-Related Factor 2
  • Thiocyanates
  • Intramolecular Oxidoreductases
  • Mif protein, mouse
  • sulforafan