Effects of different routes and forms of vitamin D administration on CD4+ T cell homeostasis and renin-angiotensin system-associated lung injury in obese mice complicated with polymicrobial sepsis

Chiu Li Yeh, Jin Ming Wu, Kuen Yuan Chen, Ming Hsun Wu, Po Jen Yang, Po Chu Lee, Po Da Chen, Sung Ling Yeh, Ming Tsan Lin

Research output: Contribution to journalArticlepeer-review

Abstract

This study investigated the impacts of enteral cholecalciferol and/or intravenous calcitriol administration on the balance of cluster of differentiation 4-positive T cell subsets, the renin-angiotensin system (RAS), and the severity of acute lung injury (ALI) in obese mice with sepsis. Mice were fed a high-fat diet and then cecal ligation and puncture (CLP) was performed. Obese mice were divided into four sepsis groups: without vitamin D (VD) (S), with oral cholecalciferol 1 d before CLP (G), with intravenous calcitriol 1 h after CLP (V), and with both cholecalciferol before and intravenous calcitriol after CLP (GV). Mice were euthanized after CLP. The V and GV groups showed higher blood T helper (Th)1/Th2 and lower Th17/T regulatory (Treg) ratios than did the S and G groups. In the lungs, The V group had the lowest nuclear factor-κB and interleukin-1β gene expressions among all groups 24 h post-CLP. In parallel, gene expressions of angiotensin type 2 receptor (AT2R), angiotensin-converting enzyme 2 (ACE2), and Mas receptor (MasR) were highest in the V group compared to other groups. The protein levels of MasR in the GV group and the AT2R/AT1R ratio in the V group were higher than those in the G and/or S groups. All of the VD-treated groups had lower injury scores than the S group. These findings suggest that calcitriol administration had more-pronounced impacts on regulating the homeostasis of Th/Treg cells and is prone to RAS-associated anti-inflammatory pathway in the lungs. However, both forms of VD attenuated sepsis-induced ALI in obese animals.

Original languageEnglish
Article number113961
JournalBiomedicine and Pharmacotherapy
Volume156
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Angiotensin receptor
  • Calcitriol
  • Cholecalciferol
  • Mas receptor
  • T helper
  • T regulatory cell

ASJC Scopus subject areas

  • Pharmacology

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