The role of estrogen signaling in a mouse model of inflammatory bowel disease: a Helicobacter hepaticus model.
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.
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America.
Lydia C
LC
Cook
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America; Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, Missouri, United States of America.
Andrew E
AE
Hillhouse
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America; IDEXX Laboratories, Columbia, Missouri, United States of America.
Matthew H
MH
Myles
Department of Biochemistry, University of Missouri, Columbia, Missouri, United States of America.
Dennis B
DB
Lubahn
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America.
Elizabeth C
EC
Bryda
Departments of Health Management and Informatics, and Statistics, University of Missouri, Columbia, Missouri, United States of America.
J Wade
JW
Davis
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America.
Craig L
CL
Franklin
D000818:Animals; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D016998:Helicobacter / Q000502:physiology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens