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 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.
Kitamura
Yoshiaki
Y
Department of Otolaryngology, Graduate School of Health-Biosciences, The University of Tokushima, Tokushima, Japan.
Das
Asish K
AK
Murata
Yuki
Y
Maeyama
Kazutaka
K
Dev
Shrabanti
S
Wakayama
Yousuke
Y
Kalubi
Bukasa
B
Takeda
Noriaki
N
Fukui
Hiroyuki
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006632:Histamine / Q000096:biosynthesis*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN
D000893:Anti-Inflammatory Agents; D006633:Histamine Antagonists; D003907:Dexamethasone; D006632:Histamine; D006640:Histidine Decarboxylase