Skip to main content
Journal cover image

Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction.

Publication ,  Journal Article
Eckhoff, DE; Smyth, CA; Eckstein, C; Bilbao, G; Young, CJ; Thompson, JA; Contreras, JL
Published in: Surgery
August 2003

BACKGROUND: The c-Jun N-terminal kinase (JNK) activation occurs after islet isolation, oxidative stress, and proinflammatory cytokine (PIC) exposure to beta-cells. Previous studies demonstrated that 17beta-estradiol modulates the activity of JNK; therefore we assessed the effects of 17beta-estradiol on JNK activation on islet survival and function after transplantation. METHODS: Isolated human pancreatic islets were incubated with PIC and 17beta-estradiol. Viability was analyzed by a colorimetric assay, islet mass by DNA content, JNK activity by Western blots, AP-1 nuclear activity with a promoter-Luciferase AP-1 responsive construct, and c-Fos, Jun-D, and ATF-2 nuclear activities by an enzyme-linked immunosorbent assay. Islet functionality was evaluated after transplantation in streptozotocin-induced diabetic NOD-SCID mice. RESULTS: The 17beta-estradiol enhanced islet viability and islet mass after exposure to PIC. A significant reduction in JNK activation occurred in islets treated with 17beta-estradiol, compared with controls, an effect partially dependent on estrogen receptors. The 17beta-estradiol induced a significant reduction in nuclear AP-1, c-fos, Jun-D, and ATF-2 activities. Animals that received 17beta-estradiol-treated islets had better islet functionality compared with saline solution-treated controls. CONCLUSIONS: The 17beta-estradiol improved isolated human pancreatic islets survival after PIC exposure by inhibition of JNK. These effects were associated with reduction in JNK targets, including the nuclear activities of transcription factors AP-1, c-Jun, c-Fos, Jun-D and ATF-2, involved in apoptosis in beta-cells. The 17beta-estradiol therapy may improve the results in clinical transplantation.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2003

Volume

134

Issue

2

Start / End Page

169 / 179

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor AP-1
  • Tissue Survival
  • Surgery
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Mitogen-Activated Protein Kinases
  • Mice, SCID
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Eckhoff, D. E., Smyth, C. A., Eckstein, C., Bilbao, G., Young, C. J., Thompson, J. A., & Contreras, J. L. (2003). Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction. Surgery, 134(2), 169–179. https://doi.org/10.1067/msy.2003.219
Eckhoff, Devin E., Cheryl A. Smyth, Christopher Eckstein, Guadalupe Bilbao, Carlton J. Young, J Anthony Thompson, and Juan L. Contreras. “Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction.Surgery 134, no. 2 (August 2003): 169–79. https://doi.org/10.1067/msy.2003.219.
Eckhoff DE, Smyth CA, Eckstein C, Bilbao G, Young CJ, Thompson JA, et al. Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction. Surgery. 2003 Aug;134(2):169–79.
Eckhoff, Devin E., et al. “Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction.Surgery, vol. 134, no. 2, Aug. 2003, pp. 169–79. Pubmed, doi:10.1067/msy.2003.219.
Eckhoff DE, Smyth CA, Eckstein C, Bilbao G, Young CJ, Thompson JA, Contreras JL. Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction. Surgery. 2003 Aug;134(2):169–179.
Journal cover image

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2003

Volume

134

Issue

2

Start / End Page

169 / 179

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor AP-1
  • Tissue Survival
  • Surgery
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Mitogen-Activated Protein Kinases
  • Mice, SCID
  • Mice
  • Male