Anti-Inflammatory Effect of Dehydroxymethylepoxyquinomicin, a Nuclear factor-κB Inhibitor, on Endotoxin-Induced Uveitis in Rats In vivo and In vitro

Ocul Immunol Inflamm. 2020;28(2):240-248. doi: 10.1080/09273948.2019.1568502. Epub 2019 Apr 5.

Abstract

Purpose: To determine the anti-inflammatory effects of dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor-κB (NF-κB) inhibitor, on endotoxin-induced uveitis (EIU) in rats.Methods: EIU was induced by a subcutaneous injection of lipopolysaccharide (LPS) in Lewis rats. DHMEQ was injected intraperitoneally concurrently with the LPS. Aqueous humor was collected 24 h after the LPS injection. Isolated peritoneal exudate cells (PECs) were exposed to LPS with or without DHMEQ to determine the production of TNF-α, IL-6, and MCP-1.Results: DHMEQ significantly reduced the number of infiltrating cells, and the concentrations of proteins, TNF-α, and IL-6 in the aqueous humor. DHMEQ suppressed the production of TNF-α, IL-6, and MCP-1 from PECs. Immunochemistry revealed a reduction in the translocation of the NF-κB p65 into the nuclei in DHMEQ-exposed PECs.Conclusions: The results indicate that DHMEQ has anti-inflammatory effects on EIU and may be a promising agent to treat intraocular inflammation.

Keywords: DHMEQ; Dexamethasone; NF-κB inhibitor; endotoxin-induced uveitis (EIU); peritoneal exudate cells (PEC).

MeSH terms

  • Animals
  • Aqueous Humor / metabolism
  • Benzamides / therapeutic use*
  • Cells, Cultured
  • Cyclohexanones / therapeutic use*
  • Disease Models, Animal
  • Immunohistochemistry
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • Rats, Inbred Lew
  • Treatment Outcome
  • Uveitis / chemically induced
  • Uveitis / diagnosis*
  • Uveitis / metabolism

Substances

  • Benzamides
  • Cyclohexanones
  • NF-kappa B
  • dehydroxymethylepoxyquinomicin