title: Arecoline increases basic fibroblast growth factor but reduces expression of IL-1, IL-6, G-CSF and GM-CSF in human umbilical vein endothelium.
abstract: BACKGROUND
  Areca nut chewing is associated with oral submucous fibrosis (OSF). Raised vascular basic fibroblast growth factor may induce fibrosis. Arecoline is a muscarinic alkaloid in areca nut, which we earlier reported causes injury and necrosis of human endothelium.
  
  
  METHODS
  Human umbilical vein endothelial cells were exposed to arecoline with or without tumor necrosis factor-α, and separately to acetylcholine, muscarine, or nicotine. Protein levels of basic fibroblast growth factor, as well as the inflammatory cytokines: granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor, and Interleukins-6, 1-α and 1-β, were determined by enzyme-linked immunosorbent assay. mRNA levels were established by real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Basic fibroblast growth factor was released into the culture medium at arecoline levels causing necrosis (P < 0.05). This contrasted with an opposite effect of arecoline on levels of the inflammatory cytokines (P < 0.05). Tumor necrosis factor-α increased IL-6 and granulocyte-macrophage colony stimulated factor, but arecoline reduced this stimulated expression (P < 0.05). Arecoline had no effect on mRNA for basic fibroblast growth factor, although there was reduced mRNA for the separate inflammatory cytokines studied. The effect of acetylcholine, muscarine, and nicotine was minimal and dissimilar to that of arecoline.
  
  
  CONCLUSIONS
  Data raise the possibility that arecoline-induced, vascular basic fibroblast growth factor contributes to OSF, by combining increased growth factor expression with endothelial necrosis, and thus driving fibroblast proliferation.
authors.affiliation: The Cellular and Molecular Pathology Research Unit, The Faculty of Dentistry, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.
authors.forename: Mafaz
authors.initials: M
authors.lastname: Ullah
authors.affiliation: The Department of Oral Surgery, The Faculty of Dentistry, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cox
authors.affiliation: The Cellular and Molecular Pathology Research Unit, The Faculty of Dentistry, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kelly
authors.affiliation: The Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Malcolm A S
authors.initials: MA
authors.lastname: Moore
authors.affiliation: The Cellular and Molecular Pathology Research Unit, The Faculty of Dentistry, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.|The Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Zoellner
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001115:Arecoline / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009116:Muscarine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D001115:Arecoline; D009538:Nicotine; D009116:Muscarine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000109:Acetylcholine
keywords: arecoline; cytokine; endothelium; fibroblast growth factor