1,25-Dihydroxyvitamin D3 and dietary vitamin D reduce inflammation in mice lacking intestinal epithelial cell Rab11a

Sayantani Goswami, Juan Flores, Iyshwarya Balasubramanian, Sheila Bandyopadhyay, Ivor Joseph, Jared Bianchi-Smak, Puneet Dhawan, Derya M. Mücahit, Shiyan Yu, Sylvia Christakos, Nan Gao

Research output: Contribution to journalArticlepeer-review

Abstract

A number of studies have examined the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 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)2D3 or dietary supplement of a high dose of vitamin D on the gut phenotypes of IEC-specific Rab11a knockout mice (Rab11aΔIEC). 1,25(OH)2D3 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.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • chemokines
  • cytokines
  • intestinal inflammation
  • NF-κB-p65
  • Rab11a
  • vitamin D

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