Toll-like receptor-2 (TLR2) is a pivotal pathogen recognition receptor that has a key role in
inflammation, diabetes, and injury.
Hyperglycemia,
inflammation, and oxidative stress induce TLR2-myeloid differentiation factor-88 (MyD88) expression and signaling, and are major pathophysiological mechanisms in the impaired diabetic wound-healing process. The aim of the study was to examine the contribution of TLR2-MyD88 expression and signaling to the prolonged
inflammation observed in diabetic
wounds. Diabetes was induced in male C57BL/6J and TLR2(-/-) mice using
streptozotocin (STZ) with matching nondiabetic mice as control. In addition, nonobese diabetic (NOD) mice were used to represent the spontaneous
type 1 diabetes condition. After 2 weeks of persistent
hyperglycemia in the mice, full-thickness excision
wounds were made on the backs aseptically. Total
RNA and
protein were subjected to real-time PCR and western blot analyses.
Wound sizes were measured using digital planimetry. TLR2
mRNA and
protein expression increased significantly in
wounds of C57BL/6J+STZ and NOD mice (P<0.05) compared with nondiabetic C57BL/6J mice. MyD88 expression,
interleukin receptor-associated kinase-1 phosphorylation, and nuclear factor-κ B (NF-κB) activation were increased in diabetic
wounds compared with nondiabetic
wounds.
Wounds of TLR2(-/-)+STZ mice showed less oxidative stress, decreased MyD88 signaling, NF-κB activation, and
cytokine secretion. The
wound closure was significant in TLR2(-/-)+ STZ mice compared with C57BL/6J+STZ mice. Collectively, our findings show that increased TLR2
mRNA and
protein expression, signaling, and activation contribute to the prolonged
inflammation in the diabetic
wounds and that absence of TLR2 may result in decreased
inflammation and improved wound healing.