title: Suppressor of cytokine signaling gene expression in human pancreatic islets: modulation by cytokines.
abstract: OBJECTIVE
  Suppressor of cytokine signaling (SOCS) proteins negatively regulate signal transduction of several cytokines. Since cytokines participate in the pancreatic islet damage in type 1 diabetes, the aim of our study was to investigate the expression of SOCS-1, -2 and -3 in isolated human islets, in basal conditions and after exposure, in vitro, to a combination of interferon (IFN)-gamma, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha cytokines and in control and in type 1 diabetic human pancreata, to establish (i) whether SOCS molecules are constitutively expressed in human pancreatic islets and (ii) whether their expression can be modulated in vitro by proinflammatory cytokines or ex vivo by an islet inflammatory process.
  
  
  METHODS
  Gene expression of SOCS-1, -2 and -3 was evaluated by RT-PCR in untreated and cytokine-treated isolated human pancreatic islets and their protein expression by immunohistochemistry in control and in type 1 diabetic human pancreata paraffin-embedded sections.
  
  
  RESULTS
  We found that SOCS-1, -2 and -3 mRNA is constitutively, although weakly, expressed in human pancreatic islets, similar to the expression observed in control pancreata by immunohistochemistry. SOCS-1, -2 and -3 mRNA expression was strongly increased in human islets after exposure, in vitro, to IFN-gamma, IL-1beta and TNF-alpha. Accordingly, an intense and islet-specific immunohistochemical staining for all three SOCS was detected in pancreata from type 1 diabetic patients.
  
  
  CONCLUSIONS
  SOCS-1, -2 and -3 genes are constitutively expressed in human pancreatic islets; their expression increases after exposure to proinflammatory cytokines and during an autoimmune inflammatory process, raising the possibility that these molecules act as key regulators of cytokine signaling in pancreatic islets.
authors.affiliation: National Center for Food Quality and Risk Assessment, Istituto Superiore di Sanita, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Santangelo
authors.forename: Angela
authors.initials: A
authors.lastname: Scipioni
authors.forename: Lorella
authors.initials: L
authors.lastname: Marselli
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
mesh_terms: D016022:Case-Control Studies; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma