title: Suppression of LPS-induced transcription and cytokine secretion by the dietary isothiocyanate sulforaphane.
abstract: METHODS
  Diets rich in cruciferous vegetables are associated with lower levels of pro-inflammatory cytokines, which may contribute to potential health-promoting properties of these vegetables. We investigate whether sulforaphane (SF), an isothiocyanate (ITC) obtained from broccoli, could suppress LPS-induced transcription and subsequent pro-inflammatory cytokine secretion at a physiologically relevant concentration using in vitro models of chronic inflammation.
  
  
  RESULTS
  We find that exposure of the LPS receptor Toll-like receptor-4 (TLR4) to physiologically appropriate concentrations of SF under non-reducing conditions results in covalent modification of cysteine residues 246 and 609. We further demonstrate that the changes in expression of 1210 genes (p ≤ 0.01) in THP-1 monocytes and the secretion of pro-inflammatory cytokines in both human peripheral blood mononuclear cells (PBMCs) and THP-1 monocytes induced by LPS exposure can be completely suppressed through exposure with physiologically appropriate concentrations of SF. Finally, we show that in vivo exposure of human PBMCs to ITCs within human circulation reduces secretion of pro-inflammatory cytokines following subsequent ex vivo LPS challenge (p < 0.001).
  
  
  CONCLUSIONS
  Covalent modification of TLR4 by ITCs and resultant suppression of LPS-induced cell signalling could lead to reductions in levels of pro-inflammatory cytokines in people with chronic diseases who consume diets rich in cruciferous vegetables.
authors.affiliation: Food and Health Programme, Institute of Food Research, Norwich, UK.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Folkard
authors.forename: Antonietta
authors.initials: A
authors.lastname: Melchini
authors.forename: Maria H
authors.initials: MH
authors.lastname: Traka
authors.forename: Ala'a
authors.initials: A
authors.lastname: Al-Bakheit
authors.forename: Shikha
authors.initials: S
authors.lastname: Saha
authors.forename: Francis
authors.initials: F
authors.lastname: Mulholland
authors.forename: Andrew
authors.initials: A
authors.lastname: Watson
authors.forename: Richard F
authors.initials: RF
authors.lastname: Mithen
mesh_terms: D001937:Brassica / Q000737:chemistry; D002460:Cell Line; D002853:Chromatography, Liquid; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D017879:Isothiocyanates / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D013454:Sulfoxides; D053719:Tandem Mass Spectrometry; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D013454:Sulfoxides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C037152:isothiocyanic acid; C016766:sulforaphane
keywords: Cruciferous vegetables; Inflammation; LPS; Sulforaphane; Toll-like receptor-4