Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats

Background: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectiv...

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Main Authors: Yoshiaki Kitamura, Asish K Das, Yuki Murata, Kazutaka Maeyama, Shrabanti Dev, Yousuke Wakayama, Bukasa Kalubi, Noriaki Takeda, Hiroyuki Fukui
Format: Article
Language:English
Published: Elsevier 2006-01-01
Series:Allergology International
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1323893015309771
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author Yoshiaki Kitamura
Asish K Das
Yuki Murata
Kazutaka Maeyama
Shrabanti Dev
Yousuke Wakayama
Bukasa Kalubi
Noriaki Takeda
Hiroyuki Fukui
author_facet Yoshiaki Kitamura
Asish K Das
Yuki Murata
Kazutaka Maeyama
Shrabanti Dev
Yousuke Wakayama
Bukasa Kalubi
Noriaki Takeda
Hiroyuki Fukui
author_sort Yoshiaki Kitamura
collection DOAJ
description Background: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectives of the present study were to examine the changes of histamine content, HDC activity and HDC mRNA expression in the nasal mucosa of allergy model rats sensitized by the exposure to toluene diisocyanate (TDI) and to investigate the effect of dexamethasone on the above mentioned allergic parameters. Methods: Rats were sensitized and provocated by TDI and the nasal allergy-like behaviors were scored during a 10 minute period after provocation. Histamine content and HDC activity in the nasal mucosa were determined using fluorometric high performance liquid chromatography. The expression of HDC mRNA in nasal mucosa was determined using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: In TDI-sensitized rats, nasal allergy-like behaviors such as sneezing and watery rhinorrhea were induced. Histamine content, HDC activity and HDC mRNA expression in nasal mucosa were also significantly increased after TDI provocation. Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats. Conclusions: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Repression of HDC gene expression and HDC activity by dexamethasone may underlie its therapeutic effect in the treatment of allergy.
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spelling doaj.art-f023a94d581b4b4fae52dfd995afd4172022-12-21T20:29:35ZengElsevierAllergology International1323-89302006-01-0155327928610.2332/allergolint.55.279Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic RatsYoshiaki Kitamura0Asish K Das1Yuki Murata2Kazutaka Maeyama3Shrabanti Dev4Yousuke Wakayama5Bukasa Kalubi6Noriaki Takeda7Hiroyuki Fukui8Department of Otolaryngology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Departments of Molecular Pharmacology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Departments of Molecular Pharmacology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Department of Pharmacology, Ehime University School of Medicine, Shigenobu, Ehime, Japan.Departments of Molecular Pharmacology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Departments of Molecular Pharmacology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Department of Otolaryngology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Department of Otolaryngology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Departments of Molecular Pharmacology, Graduate School of Health-Biosciences, the University of Tokushima, Tokushima, Japan.Background: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectives of the present study were to examine the changes of histamine content, HDC activity and HDC mRNA expression in the nasal mucosa of allergy model rats sensitized by the exposure to toluene diisocyanate (TDI) and to investigate the effect of dexamethasone on the above mentioned allergic parameters. Methods: Rats were sensitized and provocated by TDI and the nasal allergy-like behaviors were scored during a 10 minute period after provocation. Histamine content and HDC activity in the nasal mucosa were determined using fluorometric high performance liquid chromatography. The expression of HDC mRNA in nasal mucosa was determined using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: In TDI-sensitized rats, nasal allergy-like behaviors such as sneezing and watery rhinorrhea were induced. Histamine content, HDC activity and HDC mRNA expression in nasal mucosa were also significantly increased after TDI provocation. Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats. Conclusions: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Repression of HDC gene expression and HDC activity by dexamethasone may underlie its therapeutic effect in the treatment of allergy.http://www.sciencedirect.com/science/article/pii/S1323893015309771allergydexamethasoneHDChistaminerats
spellingShingle Yoshiaki Kitamura
Asish K Das
Yuki Murata
Kazutaka Maeyama
Shrabanti Dev
Yousuke Wakayama
Bukasa Kalubi
Noriaki Takeda
Hiroyuki Fukui
Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
Allergology International
allergy
dexamethasone
HDC
histamine
rats
title Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
title_full Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
title_fullStr Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
title_full_unstemmed Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
title_short Dexamethasone Suppresses Histamine Synthesis by Repressing both Transcription and Activity of HDC in Allergic Rats
title_sort dexamethasone suppresses histamine synthesis by repressing both transcription and activity of hdc in allergic rats
topic allergy
dexamethasone
HDC
histamine
rats
url http://www.sciencedirect.com/science/article/pii/S1323893015309771
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