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IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo
- Source :
- Transplant Immunology. 13:43-53
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
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-1beta, TNF-alpha and IFN-gamma. 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 beta-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.
- Subjects :
- endocrine system
medicine.medical_specialty
Immunology
Islets of Langerhans Transplantation
bcl-X Protein
Apoptosis
Biology
Cell Line
Proinflammatory cytokine
Interferon-gamma
Islets of Langerhans
Mice
In vivo
Internal medicine
medicine
Animals
Immunology and Allergy
Transplantation
geography
geography.geographical_feature_category
Dose-Response Relationship, Drug
Interleukin-6
Tumor Necrosis Factor-alpha
Pancreatic islets
Graft Survival
Islet
Up-Regulation
Endocrinology
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Cell culture
Cancer research
Cytokines
Tumor necrosis factor alpha
Interleukin-1
Subjects
Details
- ISSN :
- 09663274
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Transplant Immunology
- Accession number :
- edsair.doi.dedup.....cece4ae2e9f4ed1237c2b58197c52f6a
- Full Text :
- https://doi.org/10.1016/j.trim.2004.04.001