Abstract
Background: CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). Aim: 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). Methods: 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. Results: 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. Conclusions: 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.
Highlights
Introduction iationsThere are over 37 members of the group of A Disintegrin and Metallopeptidases (ADAMs); among them, ADAM10 and ADAM17 are functionally and structurally similar [1,2]
CXCL16 binds to immune cells that express its receptor, CXCR6, to drive them into the site of inflammation [5], and the cell membrane form that acts as a receptor internalizes oxidized low-density lipoprotein [6]
The aim of the current study is to explore the possible antidiabetic mechanism influencing RES against type 1 diabetes (T1D) induced by STZ
Summary
Introduction iationsThere are over 37 members of the group of A Disintegrin and Metallopeptidases (ADAMs); among them, ADAM10 and ADAM17 are functionally and structurally similar [1,2]. ADAM10 has a central role in cell migration, cell adhesion, and the regulation of immunity responses, in addition to controlling apoptotic process [3,4]. CXCL16 binds to immune cells that express its receptor, CXCR6, to drive them into the site of inflammation [5], and the cell membrane form that acts as a receptor internalizes oxidized low-density lipoprotein (ox-LDL) [6]. CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). 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. Results: 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
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