title: Carbon monoxide releasing molecule-3 inhibits concurrent tumor necrosis factor-α- and interleukin-1β-induced expression of adhesion molecules on human gingival fibroblasts.
abstract: OBJECTIVE
  Carbon monoxide releasing molecule-3 (CORM-3) is a newly reported compound that has shown anti-inflammatory effects in a number of cells. In this study, we aimed to investigate the influence of CORM-3 on concurrent tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced expression of adhesion molecules on human gingival fibroblasts (HGF).
  
  
  METHODS
  HGF were cultured from the explants of normal gingival tissues. Cells were costimulated with TNF-α and IL-1β in the presence or absence of CORM-3 for different periods of time. The expression of adhesion molecules, nuclear factor-kappaB (NF-κB) and phosphorylated p38 was studied using western blotting. RT-PCR was applied to check the expression of the adhesion molecules at the mRNA level. The activity of NF-κB was analysed using a reporter gene assay.
  
  
  RESULTS
  CORM-3 inhibited the up-regulation of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule in HGF after costimulation with TNF-α and IL-1β, which resulted in the decreased adhesion of peripheral blood mononuclear cells to these cells. Sustained activation of the NF-κB pathway by costimulation with TNF-α and IL-1β was suppressed by CORM-3, which was reflected by a reduced NF-κB response element-dependent luciferase activity and decreased nuclear NF-κB-p65 expression. CORM-3 inhibited MAPK p38 phosphorylation in response to stimulation with proinflammatory cytokines.
  
  
  CONCLUSIONS
  The results of this study bode well for the application of CORM-3 as an anti-inflammatory agent to inhibit NF-κB activity and to suppress the expression of adhesion molecules on HGF, which suggests a promising potential for CORM-3 in the treatment of inflammatory periodontal disease.
authors.affiliation: School of Dentistry, Shangdong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China.
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Du
authors.forename: W
authors.initials: W
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Qi
authors.forename: P
authors.initials: P
authors.lastname: Yang
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D053583:Interleukin-1beta; D016328:NF-kappa B; D009942:Organometallic Compounds; D011480:Protease Inhibitors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C476530:tricarbonylchloro(glycinato)ruthenium(II); D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases