Linking estrogen receptor β expression with inflammatory bowel disease activity.
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.
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
Marina
M
Pierdominici
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Angela
A
Maselli
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Barbara
B
Varano
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
Cristiana
C
Barbati
Digestive Endoscopy Unit, Catholic University, Rome, Italy.
Paola
P
Cesaro
Digestive Endoscopy Unit, Catholic University, Rome, Italy.
Cristiano
C
Spada
Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy.
Angelo
A
Zullo
Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy.
Roberto
R
Lorenzetti
Histopathology Complex Unit, Santo Spirito Hospital, Rome, Italy.
Marco
M
Rosati
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Gabriella
G
Rainaldi
Histopathology Complex Unit, Santo Spirito Hospital, Rome, Italy.
Maria Rosaria
MR
Limiti
IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
Luisa
L
Guidi
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Lucia
L
Conti
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Sandra
S
Gessani
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
D000911:Antibodies, Monoclonal; D016207:Cytokines; D047629:Estrogen Receptor beta; D014409:Tumor Necrosis Factor-alpha
Immune response; Immunity; Immunology and Microbiology Section; T lymphocytes; cytokines; estrogen receptors; inflammation; inflammatory bowel disease