Do immunomodulatory proteins participate in IMT504-induced islet regeneration?

LUX-LANTOS V; BIANCHI MS; CHASSEING A; MONTANER AD

Stockholm

Workshop; EMBO Workshop: Disease, Development and Stem Cells in the Pancreas; 2010

uropean Molecular Biology Organization (EMBO

We have recently shown that IMT504, a PyNTTTTGT oligonucleotide, effectively improves hyperglycemia, increases islet number and beta cells content and proliferation, and induces early expression of pancreatic progenitor markers nestin and Ngn3 in STZ diabetic rats (Diabetologia2010;53(6):1184-9). Since IMT504 has immunomodulatory properties, we evaluated the participation of the immune system in islet regeneration. We investigated the expression of proteins involved in immunomodulation and tissue remodeling, such as TSG-6 and IDO, at the time of progenitor cell expression. Male rats were i.p. injected with a single STZ dose (60 mg/kg BW) or saline (day 1). Starting on day 4, STZ animals (glycaemia: 11-20 mmol/l), were daily s.c. injected with saline (STZ and Control) or with IMT504 (4 mg/day: STZ-IMT504), and killed after two consecutive decreases in blood glucose. Pancreases were immunostained for insulin, TSG-6 and IDO. When sacrificed, STZ were frankly hyperglycaemic (24±2mM, n=6) while STZ-IMT504 had significantly lower levels (11±2mM, n=6) similar to Control (7±1mM, n=4). TSG-6 was scarcely observed in islets, without differences amongst groups. Positive staining was observed in very few lymphoid-like cells in islets and spleen. IDO expression was negligible in islets co-stained for insulin, but was positive in normal mammary gland (positive control). Since at this STZ dose inflammation does not seem to be the main cause of islet destruction, we suggest that islet regeneration is probably a consequence of IMT504 action on pancreas progenitors and beta cell proliferation, with limited participation of immunomodulatory proteins TSG-6 and IDO, at least at the time of evaluation.