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IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells.
Apoptosis. 2010 Jul; 15(7):864-76.A

Abstract

The proinflammatory cytokine, IL-1beta (Interleukin-1beta) is a significant determinant of pancreatic apoptosis and cell death that are common characteristics during diabetes. Using human derived pancreatic MIA PaCa-2 cells, we describe one of the underlying molecular mechanisms behind this observation. Incubation of these cells with IL-1beta at doses from 0.5 to 3.0 ng/ml caused significant cell death at 36 h. This was accompanied with marked increases in JNK and p38 phosphorylation together with increased levels of the endoplasmic reticulum (ER) stress markers, namely BiP, CHOP, GADD34, ATF4 and sXBP1. IL-1beta also led to increased phosphorylation of eIF2alpha and all these events could be prevented by pretreatment with the JNK inhibitor, SP600125. A time course study indicated that while IL-1beta mediated JNK phosphorylation was induced as early as 2 h of IL-1beta treatment, induction of the ER stress markers was evident at later time points. IL-1beta stimulated JNK phosphorylation was observed even in the presence of the ER stress inhibitor, 4-phenyl butyrate and the decrease in cell viability was significantly prevented in the presence of the JNK inhibitor. All these suggest that JNK activation is a pre-requisite for ER stress induction and cell death. Reports till date have consistently demonstrated JNK activation as a consequence of ER stress induction by IL-1beta in the pancreas. We show here for the first time that the activation of JNK by IL-1beta is a prelude to the subsequent induction of ER stress and cell death. These therefore suggest that the JNK-ER stress axis is critical in deciding the decreased survival status by IL-1beta in MIA PaCa-2 cells.

Authors+Show Affiliations

Institute of Genomics and Integrative Biology (IGIB), CSIR, Mall Road, Delhi, 110 007, India.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20411335

Citation

Verma, Gaurav, and Malabika Datta. "IL-1beta Induces ER Stress in a JNK Dependent Manner That Determines Cell Death in Human Pancreatic Epithelial MIA PaCa-2 Cells." Apoptosis : an International Journal On Programmed Cell Death, vol. 15, no. 7, 2010, pp. 864-76.
Verma G, Datta M. IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells. Apoptosis. 2010;15(7):864-76.
Verma, G., & Datta, M. (2010). IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells. Apoptosis : an International Journal On Programmed Cell Death, 15(7), 864-76. https://doi.org/10.1007/s10495-010-0498-4
Verma G, Datta M. IL-1beta Induces ER Stress in a JNK Dependent Manner That Determines Cell Death in Human Pancreatic Epithelial MIA PaCa-2 Cells. Apoptosis. 2010;15(7):864-76. PubMed PMID: 20411335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells. AU - Verma,Gaurav, AU - Datta,Malabika, PY - 2010/4/23/entrez PY - 2010/4/23/pubmed PY - 2010/7/8/medline SP - 864 EP - 76 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 15 IS - 7 N2 - The proinflammatory cytokine, IL-1beta (Interleukin-1beta) is a significant determinant of pancreatic apoptosis and cell death that are common characteristics during diabetes. Using human derived pancreatic MIA PaCa-2 cells, we describe one of the underlying molecular mechanisms behind this observation. Incubation of these cells with IL-1beta at doses from 0.5 to 3.0 ng/ml caused significant cell death at 36 h. This was accompanied with marked increases in JNK and p38 phosphorylation together with increased levels of the endoplasmic reticulum (ER) stress markers, namely BiP, CHOP, GADD34, ATF4 and sXBP1. IL-1beta also led to increased phosphorylation of eIF2alpha and all these events could be prevented by pretreatment with the JNK inhibitor, SP600125. A time course study indicated that while IL-1beta mediated JNK phosphorylation was induced as early as 2 h of IL-1beta treatment, induction of the ER stress markers was evident at later time points. IL-1beta stimulated JNK phosphorylation was observed even in the presence of the ER stress inhibitor, 4-phenyl butyrate and the decrease in cell viability was significantly prevented in the presence of the JNK inhibitor. All these suggest that JNK activation is a pre-requisite for ER stress induction and cell death. Reports till date have consistently demonstrated JNK activation as a consequence of ER stress induction by IL-1beta in the pancreas. We show here for the first time that the activation of JNK by IL-1beta is a prelude to the subsequent induction of ER stress and cell death. These therefore suggest that the JNK-ER stress axis is critical in deciding the decreased survival status by IL-1beta in MIA PaCa-2 cells. SN - 1573-675X UR - https://www.unboundmedicine.com/medline/citation/20411335/IL_1beta_induces_ER_stress_in_a_JNK_dependent_manner_that_determines_cell_death_in_human_pancreatic_epithelial_MIA_PaCa_2_cells_ L2 - https://doi.org/10.1007/s10495-010-0498-4 DB - PRIME DP - Unbound Medicine ER -