TLR2 expression and signaling-dependent inflammation impair wound healing in diabetic mice

Mohan R. Dasu, Ravi K. Thangappan, Alika Bourgette, Luisa A. Dipietro, Roslyn Rivkah Isseroff, Ishwarlal Jialal

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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/6JSTZ and NOD mice (P0.05) compared with nondiabetic C57BL/6J mice. MyD88 expression, interleukin receptor-associated kinase-1 phosphorylation, and nuclear factor- B (NF-B) activation were increased in diabetic wounds compared with nondiabetic wounds. Wounds of TLR2 / STZ mice showed less oxidative stress, decreased MyD88 signaling, NF-B activation, and cytokine secretion. The wound closure was significant in TLR2 / STZ mice compared with C57BL/6JSTZ 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.

Original languageEnglish (US)
Pages (from-to)1628-1636
Number of pages9
JournalLaboratory Investigation
Volume90
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • cytokines
  • inflammation
  • NF-kB
  • Toll-like receptor 2
  • type 1 diabetes
  • wound healing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

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