title: Stimulation of phagocytosis by sulforaphane.
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.
authors.affiliation: Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. hsuganu1@jhmi.edu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suganuma
authors.forename: Jed W
authors.initials: JW
authors.lastname: Fahey
authors.forename: Kelley E
authors.initials: KE
authors.lastname: Bryan
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Healy
authors.forename: Paul
authors.initials: P
authors.lastname: Talalay
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017879:Isothiocyanates; D000072019:Kelch-Like ECH-Associated Protein 1; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000235:genetics; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003470:Culture Media; D003598:Cytoskeletal Proteins; D017879:Isothiocyanates; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008263:Macrophage Migration-Inhibitory Factors; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse; C016766:sulforaphane