title: NOD2 agonist promotes the production of inflammatory cytokines in VSMC in synergy with TLR2 and TLR4 agonists.
abstract: OBJECTIVE
  To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4.
  
  
  METHODS
  Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay.
  
  
  RESULTS
  MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α.
  
  
  CONCLUSIONS
  The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Sun
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000276:immunology; D003470:Culture Media / Q000378:metabolism; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; D003470:Culture Media; D016209:Interleukin-8; D055666:Lipopeptides; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C508075:Pam(3)CSK(4) peptide; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D000119:Acetylmuramyl-Alanyl-Isoglutamine