Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS‑1 cells

Liu,Han; Yin,Jia‑Jing; Cao,Ming‑Ming; Liu,Guo‑Dong; Su,Ying; Li,Yan‑Bo

doi:10.3892/mmr.2017.7350

Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS‑1 cells

Authors:
- Han Liu
- Jia‑Jing Yin
- Ming‑Ming Cao
- Guo‑Dong Liu
- Ying Su
- Yan‑Bo Li
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Affiliations: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: August 24, 2017 https://doi.org/10.3892/mmr.2017.7350
Pages: 5787-5792
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Type 2 diabetes is a chronic inflammatory disease. Autophagy, the dynamic process of lysosomal degradation of damaged organelles and proteins, may protect β‑cells from destruction by inflammation in type 2 diabetes. The present study investigated the role of autophagy, inflammation and endoplasmic reticulum (ER) stress in type 2 diabetes. INS‑1 cells were incubated with lipopolysaccharide. The chemical chaperone 4‑phenylbutyric acid was used to inhibit ER stress, and 3‑methyadenine (3‑MA) was used to inhibit autophagy. Apoptosis was detected by flow cytometry and cell proliferation using Cell Counting kit‑8 solution. Light chain‑3B, interleukin (IL) 1β, caspase‑1 and C/EBP homologous protein production were assessed by western blotting, and rat activating transcription factor 4 and rat binding immunoglobulin heavy chain protein gene expression were determined by real‑time reverse transcription‑polymerase chain reaction. The results showed that inhibiting autophagy with 3‑MA unexpectedly contributed to cell death in β‑cells. This response was associated with an increase in inflammatory cytokines, including IL1β and caspase‑1. Inhibiting ER stress with 4‑phenylbutyric acid led to a decrease in cell apoptosis. These results showed that autophagy may have a protective effect by reducing inflammatory cytokines in β‑cells. In addition, the inositol‑requiring enzyme 1 pathway mediated the ER stress associated with autophagy and inflammatory cytokines (IL1β and caspase‑1). Therefore, inflammatory cytokines may be critical signalling nodes, which are associated with ER stress‑mediated β‑cell death.

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1	Eizirik DL and Mandrup-Poulsen T: A choice of death-the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia. 44:2115–2133. 2001. View Article : Google Scholar : PubMed/NCBI
2	Kaminitz A, Stein J, Yaniv I and Askenasy N: The vicious cycle of apoptotic beta-cell death in type 1 diabetes. Immunol Cell Biol. 85:582–589. 2007. View Article : Google Scholar : PubMed/NCBI
3	Donath MY and Shoelson SE: Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 11:98–107. 2011. View Article : Google Scholar : PubMed/NCBI
4	Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, et al: Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome. Cell Metab. 16:265–273. 2012. View Article : Google Scholar : PubMed/NCBI
5	Rabinowitz JD and White E: Autophagy and metabolism. Science. 330:1344–1348. 2010. View Article : Google Scholar : PubMed/NCBI
6	Gonzalez CD, Lee MS, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, Watada H and Wiley JW: The emerging role of autophagyin the pathophysiology of diabetes mellitus. Autophagy. 7:2–11. 2011. View Article : Google Scholar : PubMed/NCBI
7	Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI
8	Liu Y, Burgos JS, Deng Y, Srivastava R, Howell SH and Bassham DC: Degradation of the endoplasmic reticulum by autophagy during endoplasmic reticulum stress in Arabidopsis. Plant Cell. 24:4635–4651. 2012. View Article : Google Scholar : PubMed/NCBI
9	Yang X, Srivastava R, Howell SH and Bassham DC: Activation of autophagy by unfolded proteins during endoplasmic reticulum stress. Plant J. 85:83–95. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yin J Jing, Bo Li Y, Cao M Ming and Wang Y: Liraglutide improves the survival of INS-1 cells by promoting macroautophagy. Int J Endocrinol. Metab. 11:184–190. 2013.
11	Akerfeldt MC, Howes J, Chan JY, Stevens VA, Boubenna N, McGuire HM, King C, Biden TJ and Laybutt DR: Cytokine-induced beta-cell death is independent of endoplasmic reticulum stress signaling. Diabetes. 57:3034–3044. 2008. View Article : Google Scholar : PubMed/NCBI
12	Chan JY, Cooney GJ, Biden TJ and Laybutt DR: Differential regulation of adaptive and apoptotic unfolded protein response signalling by cytokine-induced nitric oxide production in mouse pancreatic beta cells. Diabetologia. 54:1766–1776. 2011. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Görgün CZ and Hotamisligil GS: Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 313:1137–1140. 2006. View Article : Google Scholar : PubMed/NCBI
15	Tang C, Koulajian K, Schuiki I, Zhang L, Desai T, Ivovic A, Wang P, Robson-Doucette C, Wheeler MB, Minassian B, et al: Glucose-induced beta cell dysfunction in vivo in rats: Link between oxidative stress and endoplasmic reticulum stress. Diabetologia. 55:1366–1379. 2012. View Article : Google Scholar : PubMed/NCBI
16	Kosacka J, Kern M, Klöting N, Paeschke S, Rudich A, Haim Y, Gericke M, Serke H, Stumvoll M, Bechmann I, et al: Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Mol Cell Endocrinol. 409:21–32. 2015. View Article : Google Scholar : PubMed/NCBI
17	Liu H, Cao MM, Wang Y, Li LC, Zhu LB, Xie GY and Li YB: Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes. Gen Comp Endocrinol. 210:124–129. 2015. View Article : Google Scholar : PubMed/NCBI
18	Imai Y, Dobrian AD, Morris MA and Nadler JL: Islet inflammation: A unifying target for diabetes treatment? Trends Endocrinol Metab. 24:351–360. 2013. View Article : Google Scholar : PubMed/NCBI
19	Böni-Schnetzler M, Thorne J, Parnaud G, Marselli L, Ehses JA, Kerr-Conte J, Pattou F, Halban PA, Weir GC and Donath MY: Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 93:4065–4074. 2008. View Article : Google Scholar : PubMed/NCBI
20	Hotamisligil GS: Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 140:900–917. 2010. View Article : Google Scholar : PubMed/NCBI
21	Quan W, Jo EK and Lee MS: Role of pancreatic β-cell death and inflammation in diabetes. Diabetes Obes Metab. 3:141–151. 2013. View Article : Google Scholar
22	Eskelinen EL and Saftig P: Autophagy: A lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 1793:664–673. 2009. View Article : Google Scholar : PubMed/NCBI