Protective Effect of Alpha-Melanocyte-Stimulating Hormone on Pancreas Islet Cell Against Peripheral Blood Mononuclear Cell-Mediated Cytotoxicity In Vitro

Abstract The α-melanocyte-stimulating hormone (α-MSH) has been shown to interact with various cells of the immune and inflammatory systems and down-regulate either the production or the action of proinflammatory cytokines. In this study, we investigated the potential of α-MSH to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from peripheral blood mononuclear cells (PBMCs) in rats. Pancreatic islets were cocultured with PBMCs in a transwell system during stimulation by phorbol myristic acid and ionomycin. α-MSH (50 nmol/L) was added to PBMCs for 2 hours before coculture. Viability and apoptosis of islets were observed by the 3-(4,5-dimethylthiazole-2-yl)-, 5-diphenyltrazolium bromide assay and flow cytometry. We measured inflammatory cytokines and nitric oxide (NO). Insulin release from islets cocultured with mononuclear cells was checked as the metric of islet function. In comparison to the control group, the viability of islets with α-MSH-treated mononuclear cells was increased and apoptosis reduced significantly. Inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β, were significantly reduced among the α-MSH-treated group. NO production in the α-MSH-treated group was decreased significantly. Insulin secretory function of the islets recovered in conditions of α-MSH treatment. This study demonstrated that α-MSH protected pancreatic islet cells from PBMC-mediated cytotoxicity and preserved insulin secretory function. This treatment may have the potential to improve graft survival in clinical islet transplantation.