Linking estrogen receptor β expression with inflammatory bowel disease activity

Oncotarget. 2015 Dec 1;6(38):40443-51. doi: 10.18632/oncotarget.6217.


Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)β expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERβ expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERβ expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERβ expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERβ downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of endoscopic disease activity.

Keywords: Immune response; Immunity; Immunology and Microbiology Section; T lymphocytes; cytokines; estrogen receptors; inflammation; inflammatory bowel disease.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology*
  • Blotting, Western
  • Caco-2 Cells
  • Case-Control Studies
  • Cell Proliferation / drug effects*
  • Colon / cytology
  • Colon / drug effects
  • Colon / metabolism
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Estrogen Receptor beta / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Remission Induction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult


  • Antibodies, Monoclonal
  • Cytokines
  • Estrogen Receptor beta
  • Tumor Necrosis Factor-alpha