SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines

Exp Biol Med (Maywood). 2015 May;240(5):631-8. doi: 10.1177/1535370214555663. Epub 2014 Oct 27.

Abstract

In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.

Keywords: Allergic inflammation; histamine; mast cells; pro-inflammatory cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cytokines / metabolism*
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Histamine Release / drug effects*
  • Hydroxyquinolines / pharmacology*
  • Hypersensitivity / prevention & control*
  • Immunoglobulin E / administration & dosage
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism*
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Passive Cutaneous Anaphylaxis
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction

Substances

  • Cytokines
  • Hydroxyquinolines
  • Inflammation Mediators
  • NF-kappa B
  • SG-HQ2
  • Immunoglobulin E
  • Gallic Acid
  • Calcium