Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats.
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.
Das
Asish Kumar
AK
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Mizuguchi
Hiroyuki
H
Kodama
Madoka
M
Dev
Shrabanti
S
Umehara
Hayato
H
Kitamura
Yoshiaki
Y
Matsushita
Chiyo
C
Takeda
Noriaki
N
Fukui
Hiroyuki
H
D000818:Animals; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D020835:Medicine, Kampo; D009297:Nasal Mucosa / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D011969:Receptors, Histamine H1 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology*
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; C090832:sho-seiryu-to; D014051:Toluene 2,4-Diisocyanate; D006632:Histamine; D006640:Histidine Decarboxylase