Genomic and non-genomic effects of glucocorticoids on allergic rhinitis model in mice

Eriko Kusaka, Mayu Sugiyama, Norie Senoo, Atsuki Yamamoto, Yukio Sugimoto

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Glucocorticoids (GCs) are well known for their anti-inflammatory effects, which are elicited through a transcriptional mechanism via a cytosolic glucocorticoid receptor (cGR)-mediated genomic effect. However, recent in vitro studies report that GCs can act as a membrane glucocorticoid receptor (mGR). This study aimed to examine whether mometasone furoate (MF) influences the nasal symptoms induced by histamine, substance P, ATP. Furthermore, the influences of various compounds on MF action were studied in vivo. The mice were intranasally administered with nasal symptom-inciting agents, and the occurrences of sneezing and nasal rubbing were counted. MF repressed the nasal symptoms caused when it was administered 10, 30 and 60 min before the induction of nasal symptoms. The repressive effect observed 10 min after the administration of MF was inhibited by RU486, a GR antagonist, but not by actinomycin D, a transcriptional inhibitor. In contrast, the repressive effect observed 60 min after the administration of MF was inhibited by RU486 and actinomycin D. Therefore, the effects observed 10 and 60 min after the MF administration were classified as non-genomic and genomic effects, respectively. The non-genomic effect suppressed the nasal symptoms induced by m-3M3FBS, a phospholipase C (PLC) activator, and was inhibited by U-73122, a PLC inhibitor. The genomic effect was inhibited by N-(p-amylcinnamoyl) anthranilic acid, a phospholipase A2 (PLA2) inhibitor. These results indicate that MF has a non-genomic effect through repression of the activation of PLC via the mGR, and MF has also a genomic effect that was influenced by the inhibition of PLA 2 through transcriptional regulation via cGR.

Original languageEnglish
Pages (from-to)279-287
Number of pages9
JournalInternational Immunopharmacology
Volume16
Issue number2
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Genomic effect
  • Glucocorticoid Mometasone furoate
  • Nasal rubbing
  • Non-genomic effect
  • Sneezing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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