Abdel-Bakky Mohamed S, Alqasoumi Abdulmajeed, Altowayan Waleed M, Amin Elham, Darwish Mostafa A
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 52471, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
Pharmaceutics. 2022 Mar 9;14(3):594. doi: 10.3390/pharmaceutics14030594.
CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). 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). 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. 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. 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.
CXCL16在被解聚素和金属蛋白酶（ADAM10）裂解后，会将T细胞吸引至炎症部位。本研究探讨了ADAM10/CXCL16/T细胞/NF-κB在1型糖尿病（T1D）发病过程中的作用，并特别提及白藜芦醇（RES）的潜在保护作用。构建了四组Balb/c小鼠：糖尿病组（腹腔注射链脲佐菌素（STZ）55 mg/kg）、给予缓冲液的对照组、RES组（腹腔注射RES 50 mg/kg）以及糖尿病+RES组（从注射STZ的第四天开始，每天腹腔注射RES（50 mg/kg）和STZ（55 mg/kg），持续12天）。分析了组织病理学变化、空腹血胰岛素（FBI）、血糖（FBG）、血清和胰腺中的ADAM10、CXCL16、NF-κB、胰腺T细胞表达、炎症和凋亡标志物。与正常小鼠相比，糖尿病小鼠的FBG、炎症和凋亡标志物、血清肿瘤坏死因子-α（TNF-α）、细胞CXCL16和ADAM10蛋白表达、胰腺T细胞迁移和NF-κB均显著增加。RES显著改善了STZ处理小鼠中扭曲的生化和炎症参数。ADAM10促进CXCL16的裂解形式，从而在T1D中将T细胞驱动至胰腺胰岛。RES成功预防了STZ造成的有害影响。ADAM10和CXCL16可能成为T1D的新型治疗靶点。
