The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

Int J Mol Sci. 2020 Jan 9;21(2):413. doi: 10.3390/ijms21020413.

Abstract

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

Keywords: EIU rat model; angiogenin; uveitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Nucleus / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endotoxins
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Male
  • Models, Biological
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Ribonuclease, Pancreatic / therapeutic use*
  • Toll-Like Receptor 4 / metabolism
  • Uveitis / chemically induced*
  • Uveitis / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Endotoxins
  • Inflammation Mediators
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • RNA, Messenger
  • Toll-Like Receptor 4
  • angiogenin
  • Ribonuclease, Pancreatic