title: Pro-apoptotic action of macrophage inhibitory cytokine 1 and counteraction of activating transcription factor 3 in carrageenan-exposed enterocytes.
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.
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Pusan, South Korea.
authors.forename: Hwi-Gon
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Juil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Seong-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Park
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Chang Gyu
authors.initials: CG
authors.lastname: Oh
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Kee Hun
authors.initials: KH
authors.lastname: Do
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology and Medical Research Institute, Pusan National University, Pusan, South Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology and Medical Research Institute, Pusan National University, Pusan, South Korea.
authors.forename: Soon Cheol
authors.initials: SC
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Yuseok
authors.initials: Y
authors.lastname: Moon
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002351:Carrageenan / Q000633:toxicity*; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005503:Food Additives / Q000633:toxicity*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D005503:Food Additives; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D008070:Lipopolysaccharides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002351:Carrageenan
keywords: ATF3; CGN; Epithelial apoptosis; MIC-1