Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2016; 22(47): 10353-10363
Published online Dec 21, 2016. doi: 10.3748/wjg.v22.i47.10353
Vitamin D differentially regulates Salmonella-induced intestine epithelial autophagy and interleukin-1β expression
Fu-Chen Huang
Fu-Chen Huang, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
Author contributions: Huang FC conceived and designed the study, analyzed and interpreted the data, and wrote the manuscript.
Supported by the Ministry of Science and Technology [MOST 103-2314-B-182-032 (in part)] and the Chang Gung Memorial Hospital, No. CMRPG8B1431, No. CMRPG8B1481 and No. CMRPG880443.
Institutional review board statement: This was an entirely in vitro study that was approved by the Chang Gung University Biosafety Committee.
Conflict-of-interest statement: The author declares that there are no financial or commercial conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Fu-Chen Huang, MD, Associate Professor, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-pei Road, Niao-sung District, Kaohsiung 833, Taiwan.
Telephone: +886-7-7317123 Fax: +886-7-7338009
Received: July 21, 2016
Peer-review started: July 25, 2016
First decision: September 7, 2016
Revised: September 21, 2016
Accepted: October 27, 2016
Article in press: October 27, 2016
Published online: December 21, 2016

To investigate the effects of active vitamin D3 on autophagy and interleukin (IL)-1β expression in Salmonella-infected intestinal epithelial cells (IECs).


Caco-2 cells, NOD2 siRNA-, Atg16L1 siRNA- or vitamin D receptor (VDR) siRNA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3 (1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR siRNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and mRNA expression, respectively. Atg16L1 siRNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mRNA expression.


The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mRNA expression, membranous Atg16L1 protein expression leading to enhanced autophagic LC3II protein expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR siRNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.


Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.

Keywords: Vitamin D, Atg16L1, Autophagy, Interleukin-1β, Salmonella, Intestinal epithelia

Core tip: In this study, the enhanced autophagy expression and down-regulation of inflammatory responses in Salmonella-infected intestinal epithelial cells by active vitamin D provide a rationale of its alternative therapy for invasive bacterial infection and other inflammatory disorders.