Altered TLR2 Expression and Signaling contribute to the Hyperinflammation in diabetic wounds

Abstract

Toll‐like receptor‐2 (TLR2) is a pivotal pathogen recognition signaling receptor and plays a key role in inflammation and injury. Hyperglycemia, inflammation, and oxidative stress induce TLR2, and are major pathophysiological mechanisms in impaired diabetic wound healing process. However, an in vivo contribution of TLR2 to the inflammatory state of diabetic wounds remains elusive. The aim of the study is to examine the contribution of TLR2 to the hyperinflammation in wounds of diabetic mice. Diabetes was induced in male C57BL/6J (WT) and TLR2 Knockout mice (KO) using streptozotocin with suitable non diabetic controls (n=6/group). Full thickness excisional wounds were made on the backs of all the mice aseptically. Total RNA and protein were subjected to RT‐PCR, Western blots, and wound sizes were recorded. TLR2 mRNA expression increased 2.5 fold in diabetic wounds of WT mice (P<0.05) with corresponding Myd88 expression, IRAK‐1phosphroylation, and NF‐κB activation compared to non diabetic wounds. Wounds of diabetic TLR2KO mice showed less lipid peroxidation (−70%), Myd88 signaling, NF‐κB(−62%), IL‐1β(−82%), and smaller wound sizes compared to diabetic WT mice after 10 days. Collectively, our findings demonstrate that increased TLR2 expression and signaling contribute to the diabetic wound hyper inflammatory state and TLR2 deficiency decreases inflammation and improves diabetic wound healing.