دورية أكاديمية
أعرض في EDS

Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency.

التفاصيل البيبلوغرافية
العنوان: Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency.
المؤلفون: Golan MA; Department of Medicine, Division of Biological Sciences, The University of Chicago, 900 E. 57th Street, KCBD 9110, Chicago, IL, 60637, USA., Liu W, Shi Y, Chen L, Wang J, Liu T, Li YC
المصدر: Digestive diseases and sciences [Dig Dis Sci] 2015 Jul; Vol. 60 (7), pp. 1941-7. Date of Electronic Publication: 2015 Apr 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Science + Business Media Country of Publication: United States NLM ID: 7902782 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2568 (Electronic) Linking ISSN: 01632116 NLM ISO Abbreviation: Dig Dis Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: 2005- : New York, NY : Springer Science + Business Media
Original Publication: New York, Plenum Pub. Corp.
مواضيع طبية MeSH: Epithelial Cells/*metabolism , Interleukin-10/*metabolism , Intestinal Mucosa/*cytology , Receptors, Calcitriol/*metabolism, Animals ; Gene Expression Regulation/physiology ; Inflammation/pathology ; Interleukin-10/genetics ; Intestinal Mucosa/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Receptors, Calcitriol/genetics
مستخلص: Background: Vitamin D deficiency is common in patients with inflammatory bowel diseases. The vitamin D receptor (VDR) is a nuclear hormone receptor mediating the activity of vitamin D hormone. Our previous studies showed that intestinal epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this activity is independent of non-epithelial immune VDR actions. Interleukin (IL)-10-deficient mouse is a chronic colitis model that develops colitis due to aberrant immune responses. Here we used IL-10 null (IL-10KO) model to assess the anti-colitic activity of epithelial VDR in the setting of an aberrant immune system.
Methods: We crossed IL-10KO mice with villin promoter-driven human (h) VDR transgenic (Tg) mice to generate IL-10KO mice that carry the hVDR transgene in intestinal epithelial cells (IL-10KO/Tg). IL-10KO and IL-10KO/Tg littermates were studied in parallel and followed for up to 25 weeks.
Results: By 25 weeks of age, accumulatively 79 % IL-10KO mice developed prolapse, whereas only 40 % IL-10KO/Tg mice did so (P < 0.001). Compared with IL-10KO mice, IL-10KO/Tg littermates showed markedly reduced mucosal inflammation in both small and large intestines, manifested by attenuation in immune cell infiltration and histological damage and a marked decrease in pro-inflammatory cytokine production. IL-10KO/Tg mice also showed reduced intestinal epithelial cell apoptosis as a result of diminished PUMA induction and caspase 3 activation.
Conclusion: These observations demonstrate that targeting hVDR expression to intestinal epithelial cells is sufficient to attenuate spontaneous colitis caused by an ill-regulated immune system, confirming a critical role of the epithelial VDR signaling in blocking colitis development.
التعليقات: Comment in: Dig Dis Sci. 2015 Jul;60(7):1871-2. (PMID: 25986526)
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معلومات مُعتمدة: P30 DK042086 United States DK NIDDK NIH HHS; R01 CA180087 United States CA NCI NIH HHS; CA180087 United States CA NCI NIH HHS; P30DK42086 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Receptors, Calcitriol)
130068-27-8 (Interleukin-10)
تواريخ الأحداث: Date Created: 20150421 Date Completed: 20150825 Latest Revision: 20181113
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4466054
DOI: 10.1007/s10620-015-3634-8
PMID: 25894930
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-2568
DOI:10.1007/s10620-015-3634-8