title: Misregulation of suppressors of cytokine signaling in eosinophilic esophagitis.
abstract: BACKGROUND
  Several findings suggest that eosinophilic esophagitis (EoE) is strongly associated with atopy and allergen-driven, Th2-type immune responses, indicating the association of EoE with immune dysregulation. The objective of this study is to ascertain the molecular mechanism involved in EoE disease development a Th2 condition.
  
  
  METHODS
  25 patients with diagnosis of EoE and 17 non-EoE controls were recruited by the gastroenterology and allergy departments from three different hospitals. Transcription analysis of suppressors of cytokine signaling 1, 3, 5 (SOCS), interleukin-5 (IL), IL-13, eotaxin (CCL26), eoataxin receptor (CCR3), and mitogen-activated protein kinase 1 (MAPK1) was performed in esophageal biopsies by real time PCR. Western blot of ERK esophageal protein and additional measures of IL-5 and VEGF levels in serum were performed.
  
  
  RESULTS
  The esophagus of EoE patients expresses and synthesizes high levels of SOCS1 and SOCS3 proteins (P < 0.05), and these expression correlated with levels of IL-5, IL-13, CCL26, CCR3, and MAPK1 genes. In addition, we demonstrate the implication of the ERK pathway (P < 0.001).
  
  
  CONCLUSIONS
  SOCS proteins probably contribute to EoE pathogenesis by directly or indirectly inducing the Th2 profile, as well as by promoting the production of Th2 cytokines. All these findings further enhance our understanding of the mechanism of EoE, and accumulating evidence suggests that EoE pathogenesis is likely to be due to misregulation of immunological pathways.
authors.affiliation: Department of Immunology, Fundación Jiménez Díaz-Capio, Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Ma Paz
authors.initials: MP
authors.lastname: Zafra
authors.forename: Natally
authors.initials: N
authors.lastname: Cancelliere
authors.forename: Pablo
authors.initials: P
authors.lastname: Rodríguez del Río
authors.forename: Mónica
authors.initials: M
authors.lastname: Ruiz-García
authors.forename: Laura
authors.initials: L
authors.lastname: Estévez
authors.forename: Victoria
authors.initials: V
authors.lastname: Andregnette
authors.forename: Silvia
authors.initials: S
authors.lastname: Sánchez-García
authors.forename: Ana
authors.initials: A
authors.lastname: Fiandor
authors.forename: Elena
authors.initials: E
authors.lastname: Collantes
authors.forename: Joaquín
authors.initials: J
authors.lastname: Sastre
authors.forename: Santiago
authors.initials: S
authors.lastname: Quirce
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ibáñez
authors.forename: Victoria
authors.initials: V
authors.lastname: del Pozo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D057765:Eosinophilic Esophagitis / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D050826:Suppressor of Cytokine Signaling Proteins