title: Analysis of the signal transduction pathway of nickel-induced matrix metalloproteinase-2 expression in the human keratinocytes in vitro: preliminary findings.
abstract: BACKGROUND
  Nickel can induce cellular and nuclear damages responsible for chronic diseases, like allergic contact dermatitis (ACD). We previously showed that matrix metalloproteinase-2 (MMP-2) gene expression was induced by nickel in nontumorigenic human keratinocytes cell line (HaCat).
  
  
  OBJECTIVE
  To investigate the signal transduction pathways involved in gelatinolytic activity induced in HaCat under nickel stimulation.
  
  
  METHODS
  We analyzed the involvement of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (PTK), nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) using specific inhibitors (H89, calphostin C, genistein, carpain and curcumin) by electrophoretic mobility shift assay, reverse transcription-polymerase chain reaction and gelatin zymography.
  
  
  RESULTS
  Our results indicate that nickel-induced MMP-2 production was inhibited with PTK, PKC and AP-1 specific inhibitors. Moreover, both PKA and NF-kB were not involved in nickel pathway.
  
  
  CONCLUSIONS
  Using HaCat, we showed that curcumin and genistein can revert nickel-induced MMP-2 upregulation. Whether the use of PTK and AP-1 inhibitors has therapeutic ramifications in the management of ACD remains to be investigated.
authors.affiliation: Microbiology and Clinical Microbiology Section, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy. sanella@libero.it
authors.forename: Brunella
authors.initials: B
authors.lastname: Perfetto
authors.forename: Monica
authors.initials: M
authors.lastname: Lamberti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Giuliano
authors.forename: Nunzia
authors.initials: N
authors.lastname: Canozo
authors.forename: Marcella
authors.initials: M
authors.lastname: Cammarota
authors.forename: Adone
authors.initials: A
authors.lastname: Baroni
mesh_terms: D002461:Cell Line, Transformed; D003474:Curcumin / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009532:Nickel / Q000633:toxicity*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007509:Irritants; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D018808:Transcription Factor AP-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C029938:nickel sulfate; D009532:Nickel; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D003474:Curcumin