The role of estrogen signaling in a mouse model of inflammatory bowel disease: a Helicobacter hepaticus model

• Published in: PloS one Vol. 9; no. 4; p. e94209
• Main Authors: Cook, Lydia C, Hillhouse, Andrew E, Myles, Matthew H, Lubahn, Dennis B, Bryda, Elizabeth C, Davis, J Wade, Franklin, Craig L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2014; Public Library of Science (PLoS)
• Subjects: Animals; Arthritis; Biology and Life Sciences; Cancer therapies; Care and treatment; CD4 antigen; Contraceptives; Crohn's Disease; Crohns disease; Cytokines; Dendritic cells; Diagnosis; Disease control; Disease Models, Animal; Estrogen Receptor alpha - deficiency; Estrogen Receptor alpha - genetics; Estrogen Receptor beta - deficiency; Estrogen Receptor beta - genetics; Estrogen receptors; Estrogens; Estrogens - metabolism; Female; Gene expression; Gene Knockout Techniques; Genetics; Health aspects; Helicobacter - physiology; Hormones; Hypotheses; Immune system; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - pathology; Intestine; Laboratory animals; Males; Medicine and Health Sciences; Menopause; Mice; Microbiota; Microbiota (Symbiotic organisms); Mucosa; Mutation; Oral contraceptives; Pathogenesis; Pregnancy; Research and Analysis Methods; Rodents; Sex hormones; Signal Transduction; Signaling; Ulcerative colitis; United States > US; Missouri
• DOI: 10.1371/journal.pone.0094209
• EISSN: 1932-6203

The pathogenesis of inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, is due in part to interactions between the immune system, genetics, the environment, and endogenous microbiota. Gonadal sex hormones (GSH), such as estrogen, are thought to be involved in the development of IBD as variations in disease severity occur during pregnancy, menopause, or oral contraceptives use. In certain strains of mice, infection with Helicobacter hepaticus triggers IBD-like mucosal inflammation that is more severe in female mice than in males, suggesting a role for GSH in this model. To determine the role of estrogen signaling in microbiota-induced intestinal inflammation, estrogen receptor (ER) α and β knock-out (KO) mice, ER agonists, and adoptive transfers were utilized. We demonstrate that, when signaling is limited to ERβ on a non-CD4+ cell subset, disease is less severe and this correlates with decreased expression of pro-inflammatory mediators.