CORM-2 Pretreatment Attenuates Inflammation-mediated Islet Dysfunction.

Abstract

During the process of human islet isolation a cascade of stressful events are triggered and negatively influence islet yield, viability, and function, including the production of proinflammatory cytokines and activation of apoptosis. Carbon monoxide-releasing molecule 2 (CORM-2) is a donor of carbon monoxide (CO) and can release CO spontaneously. Accumulating studies suggest that CORM-2 exerts cytoprotective and anti-inflammatory properties. However, the effect of CORM-2 on islet isolation is still unclear. In this study, we found that CORM-2 pretreatment significantly decreased the expression of critical inflammatory genes, including tissue factor, intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2, C-X-C motif chemokine 10, Toll-like receptor 4, interleukin-1β, interleukin-6, and tumor necrosis factor-α (TNF-α). The isolated islets of the CORM-2 pretreatment group showed reduced apoptotic rate, improved viability, and higher glucose-stimulated insulin secretion, and functional gene expression in comparison to control group. Importantly, CORM-2 pretreatment prevented the impairment caused by TNF-α, evidenced by the improved glucose-stimulated index and transplantation outcomes. The present study demonstrated the anti-inflammatory property of CORM-2 during human islet isolation, and we suggest that CORM-2 pretreatment is an appealing treatment to mitigate inflammation-mediated islet dysfunction during isolation and culture ex vivo and to preserve long-term islet survival and function.

• Authors: Xiang-Heng Cai, Guan-Qiao Wang, Rui Liang, Le Wang, Teng-Li Liu, Jia-Qi Zou, Na Liu, Yan Liu, Shu-Sen Wang, Zhong-Yang Shen
• Journal: Cell transplantation (Cell Transplant) 2020 Jan-Dec Vol. 29 Pg. 963689720903691 ISSN: 1555-3892 [Electronic] United States
• PMID: 32364405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Interleukin-1beta
• Interleukin-6
• Organometallic Compounds
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• tricarbonyldichlororuthenium (II) dimer
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Flow Cytometry
• Glucose Tolerance Test
• Humans
• Immunohistochemistry
• Inflammation (drug therapy, metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Islets of Langerhans Transplantation
• Male
• Mice, Inbred BALB C
• Organometallic Compounds (therapeutic use)
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)