title: Eotaxin and FGF enhance signaling through an extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic esophagitis.
abstract: BACKGROUND
  Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.
  
  
  METHODS
  Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8).
  
  
  RESULTS
  Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.
  
  
  CONCLUSIONS
  We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
authors.affiliation: Stanford School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Huang
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Joh
authors.forename: Judy
authors.initials: J
authors.lastname: Fuentebella
authors.forename: Anup
authors.initials: A
authors.lastname: Patel
authors.forename: Tammie
authors.initials: T
authors.lastname: Nguyen
authors.forename: Scott
authors.initials: S
authors.lastname: Seki
authors.forename: Lisa
authors.initials: L
authors.lastname: Hoyte
authors.forename: Neha
authors.initials: N
authors.lastname: Reshamwala
authors.forename: Christine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Anthony
authors.initials: A
authors.lastname: Quiros
authors.forename: Dorsey
authors.initials: D
authors.lastname: Bass
authors.forename: Eric
authors.initials: E
authors.lastname: Sibley
authors.forename: William
authors.initials: W
authors.lastname: Berquist
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cox
authors.forename: John
authors.initials: J
authors.lastname: Kerner
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
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