COMP-Ang1 promotes long-term survival of allogeneic islet grafts in a bioinert perforated chamber by inhibiting inflammation via inhibition of the TLR4 signaling pathway

Biotechnol Lett. 2016 Jun;38(6):1033-42. doi: 10.1007/s10529-016-2059-6. Epub 2016 Feb 13.

Abstract

Objectives: To evaluate the effects of cartilage oligomeric matrix protein (COMP)- angiopoietin-1 (Ang1) on allogeneic islet graft survival in a bioinert perforated chamber.

Results: COMP-Ang1 treatment significantly decreased lipopolysaccharide-induced cell apoptosis and islet-related lymph node cell proliferation (both P < 0.01). Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels in the chamber exudate were significantly lower in the COMP-Ang1 + chamber group than in the chamber group (all P < 0.05), as were the protein expression levels. COMP-Ang1 significantly inhibited the expression of Toll-like receptor 4 (TLR4) in cultured islets. Finally, full COMP-Ang1 treatment resulted in the longest survival time among the treatment groups.

Conclusion: Combined use of the bioinert perforated chamber with COMP-Ang1 is an effective strategy for improving islet allograft survival.

Keywords: Allograft; Angiopoietin-1; COMP-Ang1; Cartilage oligomeric matrix protein; Inflammation; Islet; Toll-like receptor 4; Transplantation.

MeSH terms

  • Allografts
  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cartilage Oligomeric Matrix Protein / genetics
  • Cartilage Oligomeric Matrix Protein / pharmacology*
  • Female
  • Inflammation / drug therapy
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation / instrumentation
  • Islets of Langerhans Transplantation / methods*
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Angiopoietin-1
  • Cartilage Oligomeric Matrix Protein
  • Recombinant Proteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4