Palmitic acid aggravates inflammation of pancreatic acinar cells by enhancing unfolded protein response induced CCAAT-enhancer-binding protein β–CCAAT-enhancer-binding protein α activation. (October 2016)

• Record Type: Journal Article
• Authors: Wu, Jianghong; Hu, Guoyong; Lu, Yingying; Zheng, Junyuan; Chen, Jing; Wang, Xingpeng; Zeng, Yue
• Is Part Of: International journal of biochemistry & cell biology. Volume 79(2016:Oct.)
• Page Start: 181
• Page End: 193
• Publication Date: 2016-10
• Subjects: AP acute pancreatitis -- ATF6 activating transcription factor 6 -- BSA bovine serum albumin -- CCK-8 cholecystokinin-8 -- C/EBP CCAAT-enhancer-binding protein -- CHOP CCAAT/enhancer binding protein (C/EBP) homologous protein -- eIF2 αeukaryotic translation initiation factor 2α -- EMSA electrophoretic mobility shift assays -- ER endoplasmic reticulum -- GRP78 glucose-related peptide 78 -- H&E hematoxylin and eosin -- HFD high fat diet -- HTG hypertriglyceridemia -- IκB I kappa B -- IL-6 interleukin-6 -- IRE1 inositol-requiring ER-to-nucleus signal kinase 1 -- NFκB nuclear factor kappa B -- PA palmitic acid -- PAC pancreatic acinar cell -- PERK protein kinase–like ER kinase -- 4-PBA 4-phenylbutyric acid -- SD Sprague-Dawley -- siRNA small interfering RNA -- TC total cholesterol -- TG triglycerides -- TNF-α tumor necrosis factor-alpha -- UPR unfolded protein response -- WB western blotting -- XBP-1 X-box–binding protein 1; Acute pancreatitis -- Pancreatic acinar cells -- ER stress -- NF-κB -- Inflammatory responses -- C/EBPβ; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.08.035
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: Hypertriglyceridemia aggravates acute pancreatitis with enhanced inflammatory responses in experimental acute pancreatitis model. ER stress is responsible for inflammatory responses in PA-stimulated pancreatic acinar cells. C/EBPα and C/EBPβ were activated and dependent on ER stress in PA-induced PAC injuries. C/EBPβ activation was responsible for inflammatory responses and C/EBPα activation in PA-stimulated PACs. Abstract: Hypertriglyceridemia is an independent risk factor for acute pancreatitis, in which the pathological mechanisms are not fully illustrated. Intracellular inflammatory response is a key pathological response in acute pancreatitis and endoplasmic reticulum stress has been suggested to induce inflammation and CCAAT-enhancer-binding protein expression. Therefore, the current study aims to elucidate the possible relationship between endoplasmic reticulum stress and inflammation in hypertriglyceridemia associated pancreatitis and the possible involvement of CCAAT-enhancer-binding protein. In cholecystokinin-8 stimulated rat primary acinar cells, incubation with palmitic acid caused the activation of endoplasmic reticulum stress and inflammatory responses. Pre-incubation with the chemical chaperone 4-phenylbutyric acid inhibited inflammatory responses induced by palmitic acid, whereas stimulation with the endoplasmic reticulum stress inducer thapsigargin alone induced inflammatory responses. Meanwhile we found that the transcription factors CCAAT-enhancer-binding protein α and CCAAT-enhancer-binding protein β were also induced in the palmitic acid-stimulated pancreatic acinar cells, and were similarly inhibited by 4-phenylbutyric acid pre-incubation and induced by thapsigargin stimulation alone, indicating that endoplasmic reticulum stress was responsible for CCAAT-enhancer-binding protein α and CCAAT-enhancer-binding protein β induction in the pancreatic acinar cells. Knockdown of CCAAT-enhancer-binding protein β by siRNA transfection inhibited inflammatory responses and CCAAT-enhancer-binding protein α induction but did not affect endoplasmic reticulum stress. Our study provides strong evidence that in response to palmitic acid stimulation, endoplasmic reticulum stress induces inflammatory responses in pancreatic acinar cells through induction of the CCAAT-enhancer-binding protein family, wherein CCAAT-enhancer-binding protein β activation is responsible for CCAAT-enhancer-binding protein α activation.