IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo
Autor: | Gregory L. Szot, Chung Gyu Park, Duck Jong Han, Jung Sik Kim, S.C. Kim, Seung Eun Choi, Woong-Yang Park, Curie Ahn, Chang Yong Cha, Il Hee Yoon, Kyung Mi Choi, Jin-Young Shin, Kun Ho Yoon, Jae Young Kim, Eung Soo Hwang |
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Rok vydání: | 2004 |
Předmět: |
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 |
Zdroj: | Transplant Immunology. 13:43-53 |
ISSN: | 0966-3274 |
DOI: | 10.1016/j.trim.2004.04.001 |
Popis: | 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. |
Databáze: | OpenAIRE |
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