Pro-apoptotic action of macrophage inhibitory cytokine 1 and counteraction of activating transcription factor 3 in carrageenan-exposed enterocytes

Hye Jin Choi; Hwi-Gon Kim; Juil Kim; Seong-Hwan Park; Jiyeon Park; Chang Gyu Oh; Kee Hun Do; Seung Joon Lee; Young Chul Park; Soon Cheol Ahn; Yong Sik Kim; Yuseok Moon

doi:10.1016/j.toxlet.2014.08.022

Pro-apoptotic action of macrophage inhibitory cytokine 1 and counteraction of activating transcription factor 3 in carrageenan-exposed enterocytes

Toxicol Lett. 2014 Nov 18;231(1):1-8. doi: 10.1016/j.toxlet.2014.08.022. Epub 2014 Aug 30.

Authors

Affiliations

¹ Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
² Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Pusan, South Korea.
³ Department of Microbiology and Immunology and Medical Research Institute, Pusan National University, Pusan, South Korea.
⁴ Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea.
⁵ Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea; Department of Microbiology and Immunology and Medical Research Institute, Pusan National University, Pusan, South Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Busan, South Korea. Electronic address: moon@pnu.edu.

PMID: 25180886
DOI: 10.1016/j.toxlet.2014.08.022

Abstract

Carrageenan (CGN), a widely used food additive, has been shown to injure the epithelial barrier in animal models. This type of damage is a clinical feature of inflammatory bowel disease (IBD) in humans. In the present study, the effects of CGN on pro-apoptotic responses associated with macrophage inhibitory cytokine 1 (MIC-1) regulation in human enterocytes were evaluated. CGN up-regulated the expression of MIC-1 that promoted epithelial cell apoptosis. Although MIC-1 induction was dependent on pro-apoptotic p53 protein, the pro-survival protein activating transcription factor 3 (ATF3) was negatively regulated by p53 expression. However, MIC-1 enhanced the expression of the pro-survival protein ATF3 in enterocytes exposed to CGN. Functionally, MIC-1-mediated epithelial cell apoptosis was counteracted by the pro-survival action of ATF3 in response to CGN exposure. These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress.

Keywords: ATF3; CGN; Epithelial apoptosis; MIC-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Activating Transcription Factor 3 / metabolism*
Animals
Apoptosis / drug effects*
Carrageenan / toxicity*
Enterocytes / drug effects*
Enterocytes / metabolism
Enterocytes / pathology
Food Additives / toxicity*
Growth Differentiation Factor 15 / metabolism*
HCT116 Cells
Humans
Lipopolysaccharides / pharmacology
Male
Mice
Mice, Inbred C57BL
RNA Interference
Signal Transduction / drug effects
Time Factors
Transfection
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

ATF3 protein, human
Activating Transcription Factor 3
Atf3 protein, mouse
Food Additives
GDF15 protein, human
Gdf15 protein, mouse
Growth Differentiation Factor 15
Lipopolysaccharides
TP53 protein, human
Tumor Suppressor Protein p53
Carrageenan