title: [Mechanism of carbon monoxide affecting the expression of cellular adhesion molecule under stimulation of inflammatory cytokines to human gingival fibroblasts].
abstract: OBJECTIVE
  To investigate the mechanism by which carbon monoxide inhibits the expression of adhesion molecules on human gingival fibroblasts (HGF) stimulated with inflammatory cytokines.
  
  
  METHODS
  HGF were cultured in vitro, and stimulated with 50 ng x mL tumor necrosis factor-alpha (TNF-alpha) and 10 ng x mL(-1) interleukin-1beta (IL-1beta) concurrently in the presence or absence of carbon monoxide releasing molecule-3 (CORM-3) at 500 micromol x L-1. Expression of phosphorylated extracellular regulated protein kinase (ERK), phosphorylated c-Jun N-terminal kinase (NK) and phosphorylated p38 in mitogen-activated protein kinase(MAPK) pathway was studied by Western blot at 10 min and 20 min, respectively. Nuclear expression of nuclear factor-kappaB (NF-kappaB) was checked by Western blot after 4 h stimulation. In some experiments, cells were prestimulated by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ) for 8 h before cytokine stimulation and the expression of intercellular adhesion molecule-1 (ICAM-1) was checked by Western blot after 24 h.
  
  
  RESULTS
  CORM-3 significantly inhibited the phosphorylation of MAPK p38 after 10 min stimulation with cytokines, but had no signifi-cant effect on the phosphorylation of ERK and JNK. CORM-3 significantly inhibited the nuclear expression of NF-KB-p65 on HGF after 4 h stimulation by inflammatory cytokines. The inhibitory effect of CORM-3 on the expression of ICAM-1 was not influenced by guanylate cyclase inhibitor ODQ.
  
  
  CONCLUSIONS
  The inhibitory effect of carbon monoxide on the expression of adhesion molecules might be exerted by its inhibitory effect on the NF-kappaB activity and MAPK p38 phosphorylation.
authors.affiliation: Dept. of Oral and Maxillofacial Surgery, Stomatology Hospital of Shandong University, Jinan 250012, China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Hou
authors.forename: Lingling
authors.initials: L
authors.lastname: Wei
authors.forename: Pingping
authors.initials: P
authors.lastname: Mu
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.forename: Pishan
authors.initials: P
authors.lastname: Yang
mesh_terms: D002248:Carbon Monoxide; D016207:Cytokines; D005347:Fibroblasts; D005881:Gingiva; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002248:Carbon Monoxide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases