Resveratrol inhibits macrophage infiltration of pancreatic islets in streptozotocin-induced type 1 diabetic mice via attenuation of the CXCL16/NF-κΒ p65 signaling pathway.

AIM

Despite CXC chemokine ligand 16 (CXCL16) contributes to the pathogenesis of many inflammatory disorders, the mechanism by which CXCL16 is involved in T1DM remains unclear. In this study, we examined the role of the CXCL16/NF-κΒ p65 signaling pathway in the progression of this disease and the possible protective effect of resveratrol (RES) on streptozotocin (STZ)-induced T1DM.

MAIN METHODS

Mice were classified into four groups of 10 animals each. The control group received citrate buffer. The RES group received 50 mg/kg i.p. RES for 12 days beginning on day 4 of citrate buffer. The STZ group received 55 mg/kg i.p. STZ once a day for 5 consecutive days. The fourth group injected with RES (50 mg/kg) for 12 days starting on day 4 of STZ injection. Biochemical, physical and oxidative stress parameters were measured in all groups. Moreover, expression of CXCL16 and CD45 was measured in pancreatic islets and spleen. Additionally, NF-κΒ p65 was investigated in isolated islets.

KEY FINDINGS

Our results showed a significant elevation of CXCL16, NF-κΒ p65 and CD45 in islets of diabetic (DM) mice. Intriguingly, RES significantly restored distorted biochemical, physical and oxidative stress parameters after STZ treatment as well as inhibited the expression of CXCL16/NF-κΒ p65 in pancreatic islets. Moreover, RES normalized CXCL16 and CD45 expression in islets and spleen.

SIGNIFICANCE

This study demonstrates first evidence that CXCL16/NF-κΒ p65 signaling pathway is associated with macrophage infiltration to pancreatic islet in T1DM and that RES successfully improved T1DM may be at least via inhibiting this pathway.