title: Pro-inflammatory cytokines induce suppressor of cytokine signaling-3 in human periodontal ligament cells.
abstract: BACKGROUND
  Periapical inflammation is initiated by insult to the dental pulp and mediated by inflammatory cytokines in the periodontal tissue. On the other hand, the destruction of tissue can be prevented by the suppression of pro-inflammatory cytokine activity. The balance between these cytokines and their counterregulatory molecules has been suggested to regulate tissue destruction. Suppressors of cytokine signaling (SOCS) proteins are known to suppress inflammatory cytokine signaling via the classic negative feedback loop. However, the mechanism by which they are induced by inflammatory cytokines and regulated during the development of periodontal disease remains to be clarified. We investigated the effects of inflammatory cytokines on SOCS protein expression and their signaling pathways in human periodontal ligament (PDL) cells.
  
  
  METHODS
  We examined the effect of inflammatory cytokines on SOCSs expression and its signaling pathway in human PDL cells using reverse transcription- and real-time polymerase chain reaction, Western blot methods. Furthermore, we also examined whether these cytokines-induced SOCS-3 suppress chemokines secretion using ELISA methods.
  
  
  RESULTS
  We found that inflammatory cytokines interleukin (IL)-1beta and IL-6 induced expression of SOCS-3 but not that of SOCS-2 in human PDL cells. IL-1beta and IL-6 simultaneously induced IL-8 and monocyte chemoattractant protein-1 secretion in PDL cells, whereas SOCS-3 overexpression suppressed secretion of these chemokines through inhibition of phosphorylation in downstream signaling.
  
  
  CONCLUSIONS
  The results suggest that pro-inflammatory cytokines induced SOCS-3 expression. The SOCS-3 induction suggests playing an important role in negative feedback, suppressing serious destruction of periodontal tissue in apical periodontitis through a chemokine-dependent mechanism.
authors.affiliation: Department of Odontology, Fukuoka Dental College, Fukuoka, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Fukushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
authors.forename: Toshio
authors.initials: T
authors.lastname: Izumi
authors.forename: Chieko
authors.initials: C
authors.lastname: Shigeyama
authors.forename: Koji
authors.initials: K
authors.lastname: Okabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Anan
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology; D053612:Janus Kinases / Q000032:analysis / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000276:immunology; D010513:Periodontal Ligament / Q000166:cytology / Q000276:immunology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases