Effects of a selective casein kinase 1δ and ε inhibitor on FcεRI expression and IgE-mediated immediate-type cutaneous reactions in dogs

J Vet Med Sci. 2019 Dec 5;81(11):1680-1684. doi: 10.1292/jvms.18-0756. Epub 2019 Oct 2.

Abstract

The molecular clock network in mast cells has been shown to be a factor responsible for circadian regulation of allergic inflammation. PF670462 is a selective inhibitor of casein kinase 1δ and ε (CK1δ/ε) that control the posttranslational modification of clock proteins. The aims of this study were to evaluate the effects of PF670462 on gene and protein expression of FcεRI, the high-affinity IgE receptor, in canine mast cells and on IgE-mediated immediate-type cutaneous reactions in dogs. PF670462 decreased mRNA expression of FcεRIα and β, but not γ, and protein expression of FcεRI in a canine mast cell line. Furthermore, PF670462 suppressed IgE-mediated immediate-type cutaneous erythema in dogs. These findings indicate that CK1δ/ε function as regulators for FcεRI expression and IgE-mediated cutaneous reactions in dogs.

Keywords: IgE; circadian rhythm; dog; mast cell.

MeSH terms

  • Anaphylaxis
  • Animals
  • Casein Kinase Idelta / antagonists & inhibitors*
  • Casein Kinase Iepsilon / genetics
  • Casein Kinase Iepsilon / metabolism*
  • Dog Diseases / genetics
  • Dog Diseases / metabolism*
  • Dogs
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Immunoglobulin E / metabolism*
  • Mast Cells / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • Receptors, IgE
  • Immunoglobulin E
  • PF-670462
  • Casein Kinase Idelta
  • Casein Kinase Iepsilon