Alpha-melanocyte stimulating hormone preserves islet graft survival through down-regulation of Toll-like receptors

Transplantation Proceedings
E-J JungD-J Han

Abstract

The induction of Toll-like receptors (TLRs) in β cells is involved in β-cell death and graft rejection after transplantation. This study investigated the ability of alpha-melanocyte stimulating hormone (α-MSH) to protect pancreatic islets and improve graft survival through regulation of TLRs. To test the effect of α-MSH on TLR regulation, we first isolated pancreatic islets from rats pretreated with/without α-MSH and assayed inflammatory cytokines and insulin release, and measured the expression of TLRs. Pancreatic islets were transplanted into the kidney capsule of a diabetes mellitus (DM) mouse with and without prior injection of α-MSH. The blood glucose levels were measured and TLR4 expression in transplanted kidney tissue was assessed. Islet morphology, including size and total mass, was improved in the α-MSH group compared to the control group. The expression of TLRs as well as nitric oxide and monocyte chemoattractant protein 1 production were decreased in islets isolated from α-MSH-treated rats. In DM mice, the normoglycemic ratio was higher in the α-MSH-treated group than in the sham group. Moreover, the high levels of TLR4 expression observed in DM kidney tissue were significantly decreased in islet-transplanted tissue...Continue Reading

References

Sep 3, 2010·European Journal of Immunology·Bernd KrügerBernd Schröppel

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