IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

Seung Eun Choi; Kyung Mi Choi; Il Hee Yoon; Jin Young Shin; Jung Sik Kim; Woong Yang Park; Duck Jong Han; Song Chul Kim; Curie Ahn; Jae Young Kim; Eung Soo Hwang; Chang Yong Cha; Gregory L. Szot; Kun Ho Yoon; Chung Gyu Park

doi:10.1016/j.trim.2004.04.001

IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

Seung Eun Choi
, Kyung Mi Choi
, Il Hee Yoon
, Jin Young Shin
, Jung Sik Kim
, Woong Yang Park
, Duck Jong Han
, Song Chul Kim
, Curie Ahn
, Jae Young Kim
, Eung Soo Hwang
, Chang Yong Cha
, Gregory L. Szot
, Kun Ho Yoon
, Chung Gyu Park

Division of Endocrinology & Metabolism

Seoul National University
University of Ulsan
University of California at San Francisco

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

Abstract

Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1β, TNF-α and IFN-γ. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or β-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.

Original language	English
Pages (from-to)	43-53
Number of pages	11
Journal	Transplant Immunology
Volume	13
Issue number	1
DOIs	https://doi.org/10.1016/j.trim.2004.04.001
State	Published - Jun 2004

Bibliographical note

Funding Information:
This work was supported partly by Good Health R&D Project grant (HMP-01-PJ1-PG1-01CH09-0006) of the Ministry of Health and Welfare, Republic of Korea and partly by a grant from the Seoul National University Hospital Research Fund. We gratefully acknowledge Dr Jeffrey A. Bluestone for critical review and discussion of the work, Dr Ju-Han Kim for oligonucleotide microarray data analysis, and Dr Daehee Kang and Kyung-Moo Lee for the statistical data analysis.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Apoptosis
IL-6
Islet transplantation
Pancreatic islet beta cell
Protection

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10.1016/j.trim.2004.04.001

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Choi, S. E., Choi, K. M., Yoon, I. H., Shin, J. Y., Kim, J. S., Park, W. Y., Han, D. J., Kim, S. C., Ahn, C., Kim, J. Y., Hwang, E. S., Cha, C. Y., Szot, G. L., Yoon, K. H., & Park, C. G. (2004). IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo. Transplant Immunology, 13(1), 43-53. https://doi.org/10.1016/j.trim.2004.04.001

@article{59b2f4e9037d4428ba0fac6e6520b157,

title = "IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo",

abstract = "Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1β, TNF-α and IFN-γ. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or β-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.",

keywords = "Apoptosis, IL-6, Islet transplantation, Pancreatic islet beta cell, Protection",

author = "Choi, \{Seung Eun\} and Choi, \{Kyung Mi\} and Yoon, \{Il Hee\} and Shin, \{Jin Young\} and Kim, \{Jung Sik\} and Park, \{Woong Yang\} and Han, \{Duck Jong\} and Kim, \{Song Chul\} and Curie Ahn and Kim, \{Jae Young\} and Hwang, \{Eung Soo\} and Cha, \{Chang Yong\} and Szot, \{Gregory L.\} and Yoon, \{Kun Ho\} and Park, \{Chung Gyu\}",

note = "Funding Information: This work was supported partly by Good Health R\&D Project grant (HMP-01-PJ1-PG1-01CH09-0006) of the Ministry of Health and Welfare, Republic of Korea and partly by a grant from the Seoul National University Hospital Research Fund. We gratefully acknowledge Dr Jeffrey A. Bluestone for critical review and discussion of the work, Dr Ju-Han Kim for oligonucleotide microarray data analysis, and Dr Daehee Kang and Kyung-Moo Lee for the statistical data analysis.",

year = "2004",

month = jun,

doi = "10.1016/j.trim.2004.04.001",

language = "English",

volume = "13",

pages = "43--53",

journal = "Transplant Immunology",

issn = "0966-3274",

publisher = "Elsevier B.V.",

number = "1",

}

Choi, SE, Choi, KM, Yoon, IH, Shin, JY, Kim, JS, Park, WY, Han, DJ, Kim, SC, Ahn, C, Kim, JY, Hwang, ES, Cha, CY, Szot, GL, Yoon, KH & Park, CG 2004, 'IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo', Transplant Immunology, vol. 13, no. 1, pp. 43-53. https://doi.org/10.1016/j.trim.2004.04.001

TY - JOUR

T1 - IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

AU - Choi, Seung Eun

AU - Choi, Kyung Mi

AU - Yoon, Il Hee

AU - Shin, Jin Young

AU - Kim, Jung Sik

AU - Park, Woong Yang

AU - Han, Duck Jong

AU - Kim, Song Chul

AU - Ahn, Curie

AU - Kim, Jae Young

AU - Hwang, Eung Soo

AU - Cha, Chang Yong

AU - Szot, Gregory L.

AU - Yoon, Kun Ho

AU - Park, Chung Gyu

N1 - Funding Information: This work was supported partly by Good Health R&D Project grant (HMP-01-PJ1-PG1-01CH09-0006) of the Ministry of Health and Welfare, Republic of Korea and partly by a grant from the Seoul National University Hospital Research Fund. We gratefully acknowledge Dr Jeffrey A. Bluestone for critical review and discussion of the work, Dr Ju-Han Kim for oligonucleotide microarray data analysis, and Dr Daehee Kang and Kyung-Moo Lee for the statistical data analysis.

PY - 2004/6

Y1 - 2004/6

N2 - Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1β, TNF-α and IFN-γ. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or β-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.

AB - Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1β, TNF-α and IFN-γ. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or β-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.

KW - Apoptosis

KW - IL-6

KW - Islet transplantation

KW - Pancreatic islet beta cell

KW - Protection

UR - https://www.scopus.com/pages/publications/2942564469

U2 - 10.1016/j.trim.2004.04.001

DO - 10.1016/j.trim.2004.04.001

M3 - Article

C2 - 15203128

AN - SCOPUS:2942564469

SN - 0966-3274

VL - 13

SP - 43

EP - 53

JO - Transplant Immunology

JF - Transplant Immunology

IS - 1

ER -

IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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