title: Eotaxin-3 (CCL26) Expression in Human Pancreatic Myofibroblasts.
abstract: OBJECTIVE
  Eosinophil infiltration is a histological feature of autoimmune pancreatitis (AIP). However, little is known about the mechanisms underlying eosinophilic infiltration. In this study, we aimed to investigate the expression of the eosinophil chemotactic protein, eotaxin-3, in human pancreatic myofibroblasts.
  
  
  METHODS
  Enzyme-linked immunosorbent assays and quantitative polymerase chain reactions were used to quantify eotaxin-3 protein and messenger RNA levels, respectively.
  
  
  RESULTS
  Eotaxin-3 expression was induced by T helper type 2 cytokines, interleukin-4 (IL-4) and IL-13, in time- and dose-dependent manners. Both IL-4 and IL-13 induced the rapid phosphorylation of STAT6 (signal transducer and activator of transcription 6), and STAT6-specific small interfering RNA significantly blocked IL-4- and IL-13-induced eotaxin-3 expression, indicating involvement of STAT6 signaling pathways in eotaxin-3 induction. In contrast, SOCS (suppressor of cytokine signaling) protein-specific small interfering RNA experiments suggested that the SOCS family proteins are negative regulators of IL-4- and IL-13-induced eotaxin-3 expression in pancreatic myofibroblasts. Interferon-γ significantly inhibited IL-4- and IL-13-induced eotaxin-3 expression, and this response was mediated by STAT1 activation.
  
  
  CONCLUSIONS
  Pancreatic myofibroblasts may be a cellular source of eotaxin-3 in the pancreas. The T helper type 2 cytokines, IL-4 and IL-13, are critical factors for the induction of eotaxin-3 in the pancreas.
authors.affiliation: From the *Departments of Medicine and †Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Takehide
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Shioya
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Bamba
authors.forename: Hisanori
authors.initials: H
authors.lastname: Shiomi
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D058628:Myofibroblasts / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4