Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats

Allergol Int. 2009 Mar;58(1):81-8. doi: 10.2332/allergolint.O-07-526. Epub 2008 Dec 1.

Abstract

Background: The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats.

Methods: Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 microl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR.

Results: SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13.

Conclusions: These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Histamine / physiology*
  • Histidine Decarboxylase / genetics
  • Hypersensitivity / drug therapy*
  • Male
  • Medicine, Kampo*
  • Nasal Mucosa / drug effects
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred BN
  • Receptors, Histamine H1 / genetics
  • Signal Transduction / drug effects*
  • Toluene 2,4-Diisocyanate / pharmacology*

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • RNA, Messenger
  • Receptors, Histamine H1
  • sho-seiryu-to
  • Toluene 2,4-Diisocyanate
  • Histamine
  • Histidine Decarboxylase