Abstract

CTLA–4 protein expressed on activated T–cells is an important mole-cule involved in T-cell homeostasis and mutations in CTLA–4 gene have been linked with autoimmune diseases such as type 1 diabetes mellitus (T1DM). T1DM is caused by selective destruction of pancreatic β–cells and its onset is characterized by infiltration and accumulation of T–cells in pancreatic tissue until the trigger of autoimmune destruction of β–cells is activated. As a negative regulator of T–cell activation, the CTLA–4 gene expression may result in suppression of T1DM development. This study was carried out to assess the role of CTLA–4 gene in amelioration of alloxan–induced T1DM in rats treated with ethanolic extracts of Allium sativum. This study involved 40 adult male Wistar rats divided into five groups: Group 1 was the control while groups 2-5 were induced with a single intraperitoneal dose of alloxan (120mg/kg). Groups 3-5 were treated for 21 days with 100, 250 and 500mg/kg ethanolic extracts of A. sativum respectively. After the study period, experimental animals were sacrificed; pancreatic tissue was harvested for histological study. Blood was collected for genomic DNA extraction and CTLA–4 gene amplification done using polymerase chain reaction (PCR). The PCR amplicons were run through agarose gel to produce visible DNA bands and 1kb plus DNA ladder was used as DNA molecular weight marker. The result showed regeneration of pancreatic parenchyma and islet cells in diabetic animals treated with ethanolic extracts of A. sativum. The observed up-regulation of CTLA–4 gene expression in treated animals is believed to contribute to down-regulation of auto-immune responses triggered by alloxan exposure and inhibit selective destruction of β-cell of pancreatic islets. Hence, activation of CTLA-4 gene may contribute to inhibition of onset and progression of auto-immune diseases such as type 1 diabetes mellitus.

Key words: Allium sativum, CTLA-4 gene, Diabetic rats