Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice

• Egile Nagusiak: Mohamed S. Abdel-Bakky (Egilea), Abdulmajeed Alqasoumi (Egilea), Waleed M. Altowayan (Egilea), Elham Amin (Egilea), Mostafa A. Darwish (Egilea)
• Formatua: Liburua
• Argitaratua: MDPI AG, 2022-03-01T00:00:00Z.
• Gaiak: article
• Sarrera elektronikoa: Connect to this object online.
• Notes: 10.3390/pharmaceutics14030594; 1999-4923
• Keywords: CXCL16; ADAM10; NF-κβ; apoptosis; pancreatic islets; resveratrol; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 3, p 594 (2022)

<b>Background:</b> CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). <b>Aim:</b> The current study explored the role of ADAM10/CXCL16/T-cell/NF-κB in the initiation of type 1 diabetes (T1D) with special reference to the potential protecting role of resveratrol (RES). <b>Methods:</b> Four sets of Balb/c mice were created: a diabetes mellitus (DM) group (streptozotocin (STZ) 55 mg/kg, i.p.], a control group administered buffer, a RES group [RES, 50 mg/kg, i.p.), and a DM + RES group (RES (50 mg/kg, i.p.) and STZ (55 mg/kg, i.p.) administered daily for 12 days commencing from the fourth day of STZ injection). Histopathological changes, fasting blood insulin (FBI), glucose (FBG), serum and pancreatic ADAM10, CXCL16, NF-κB, T-cells pancreatic expression, inflammatory, and apoptotic markers were analyzed. <b>Results:</b> FBG, inflammatory and apoptotic markers, serum TNF-α, cellular CXCL16 and ADAM10 protein expression, pancreatic T-cell migration and NF-κB were significantly increased in diabetic mice compared to normal mice. RES significantly improved the biochemical and inflammatory parameters distorted in STZ-treated mice. <b>Conclusions:</b> ADAM10 promotes the cleaved form of CXCL16 driving T-cells into the islets of the pancreatic in T1D. RES successfully prevented the deleterious effect caused by STZ. ADAM10 and CXCL16 may serve as novel therapeutic targets for T1D.