1,25‐Dihydroxyvitamin D 3 and dietary vitamin D reduce inflammation in mice lacking intestinal epithelial cell Rab11a
Autor: | Ivor Joseph, Shiyan Yu, Sheila Bandyopadhyay, Jared Bianchi-Smak, Sylvia Christakos, Juan Flores, Iyshwarya Balasubramanian, Sayantani Goswami, Derya M. Mücahit, Nan Gao, Puneet Dhawan |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Chemokine Physiology medicine.medical_treatment Clinical Biochemistry Inflammation Proinflammatory cytokine Enteritis 03 medical and health sciences 0302 clinical medicine Immune system Internal medicine medicine Vitamin D and neurology biology business.industry Cell Biology medicine.disease 030104 developmental biology Endocrinology Cytokine 030220 oncology & carcinogenesis Knockout mouse biology.protein medicine.symptom business |
Zdroj: | Journal of Cellular Physiology. 236:8148-8159 |
ISSN: | 1097-4652 0021-9541 |
Popis: | A number of studies have examined the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) on intestinal inflammation driven by immune cells, while little information is currently available about its impact on inflammation caused by intestinal epithelial cell (IEC) defects. Mice lacking IEC-specific Rab11a a recycling endosome small GTPase resulted in increased epithelial cell production of inflammatory cytokines, notably IL-6 and early onset of enteritis. To determine whether vitamin D supplementation may benefit hosts with epithelial cell-originated mucosal inflammation, we evaluated in vivo effects of injected 1,25(OH)2 D3 or dietary supplement of a high dose of vitamin D on the gut phenotypes of IEC-specific Rab11a knockout mice (Rab11aΔIEC ). 1,25(OH)2 D3 administered at 25 ng, two doses per mouse, by intraperitoneal injection, reduced inflammatory cytokine production in knockout mice compared to vehicle-injected mice. Remarkably, feeding mice with dietary vitamin D supplementation at 20,000 IU/kg spanning fetal and postnatal developmental stages led to improved bodyweights, reduced immune cell infiltration, and decreased inflammatory cytokines. We found that these vitamin D effects were accompanied by decreased NF-κB (p65) in the knockout intestinal epithelia, reduced tissue-resident macrophages, and partial restoration of epithelial morphology. Our study suggests that dietary vitamin D supplementation may prevent and limit intestinal inflammation in hosts with high susceptibility to chronic inflammation. |
Databáze: | OpenAIRE |
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