title: The investigation of synovial genomic targets of bucillamine with microarray technique.
abstract: OBJECTIVE
  To identify the molecular mechanisms of bucillamine activity, global gene expression analysis and pathway analysis were conducted using IL-1 beta-stimulated human fibroblast-like synovial cells (FLS).
  
  
  METHODS
  Normal human FLS were treated with IL-1 beta in the presence or absence of 10 and 100 microM bucillamine for 6 h. Total RNA was extracted and global gene expression levels were detected using a 44 k human whole genome array. Data were analyzed using Ingenuity pathway analysis.
  
  
  RESULTS
  Numerous pathways were activated by IL-1 beta stimulation. At both concentrations, bucillamine suppressed nine signal pathways stimulated by IL-1 beta.
  
  
  CONCLUSIONS
  Bucillamine effectively inhibited fibroblast growth factor (FGF) signaling and tight junction signaling activated by IL-1 beta in FLS. Suppression of these signal pathways may correlate with the pharmacologic mechanisms of bucillamine. In particular, the suppression of FGF signaling by bucillamine is remarkable because the activation of FGF signaling may be involved in rheumatoid arthritis pathology.
authors.affiliation: Research & Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma-shi, Nara, 630-0101, Japan. kenji.oki@santen.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.forename: Fumio
authors.initials: F
authors.lastname: Tsuji
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kageyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aono
authors.forename: Minoru
authors.initials: M
authors.lastname: Sasano
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D046228:Microarray Analysis / Q000379:methods*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D003545:Cysteine; C026535:bucillamine