title: Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease.
abstract: During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4 hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6 microM nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and 6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24 hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4 hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4 hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine.
authors.affiliation: Department of Dermatology, Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Aylin
authors.initials: A
authors.lastname: Kalayciyan
authors.forename: Helmut
authors.initials: H
authors.lastname: Orawa
authors.forename: Sabine
authors.initials: S
authors.lastname: Fimmel
authors.forename: Frank H
authors.initials: FH
authors.lastname: Perschel
authors.forename: José-B
authors.initials: JB
authors.lastname: González
authors.forename: Rudolf G
authors.initials: RG
authors.lastname: Fitzner
authors.forename: Constantin E
authors.initials: CE
authors.lastname: Orfanos
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001528:Behcet Syndrome / Q000097:blood / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012906:Smoke; D013859:Thiocarbamates / Q000494:pharmacology; D014026:Nicotiana; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016209:Interleukin-8; D012906:Smoke; D013859:Thiocarbamates; D042461:Vascular Endothelial Growth Factor A; C066229:prolinedithiocarbamate; D009538:Nicotine; D011392:Proline; D019833:Genistein; C004541:biochanin A