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.
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.
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