Oncotarget

Research Papers: Immunology:

Linking estrogen receptor β expression with inflammatory bowel disease activity

Marina Pierdominici, Angela Maselli, Barbara Varano, Cristiana Barbati, Paola Cesaro, Cristiano Spada, Angelo Zullo, Roberto Lorenzetti, Marco Rosati, Gabriella Rainaldi, Maria Rosaria Limiti, Luisa Guidi, Lucia Conti and Sandra Gessani _

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Oncotarget. 2015; 6:40443-40451. https://doi.org/10.18632/oncotarget.6217

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Abstract

Marina Pierdominici1, Angela Maselli2, Barbara Varano3, Cristiana Barbati1, Paola Cesaro4, Cristiano Spada4, Angelo Zullo5, Roberto Lorenzetti5, Marco Rosati6, Gabriella Rainaldi3, Maria Rosaria Limiti6, Luisa Guidi7, Lucia Conti3,* and Sandra Gessani3,*

1 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

2 Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy

3 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

4 Digestive Endoscopy Unit, Catholic University, Rome, Italy

5 Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy

6 Histopathology Complex Unit, Santo Spirito Hospital, Rome, Italy

7 IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy

* These authors jointly supervised this work

Correspondence to:

Lucia Conti, email:

Sandra Gessani, email:

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

Received: September 08, 2015 Accepted: October 02, 2015 Published: October 22, 2015

Abstract

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.


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