Abstract | BACKGROUND: METHODS: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR. RESULTS: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p < 0.001 in 30 min, respectively) in severe AR mice relative to that in controls. Mechanistically, we postulate that GALR2 is expressed in B cells, and M871 administration reduces IgE production, as well as the number of B cells in tissues. CONCLUSIONS: GAL signaling may not change progressively with increasing nasal sensitization, suggesting that this signaling process exacerbates, rather than directly trigger, AR. GAL-GALR2 signaling likely mediates AR development, suggesting that its inhibition represents a novel therapeutic strategy for AR.
|
Authors | Michitsugu Kawada, Hidenori Yokoi, Toru Kimura, Yuma Matsumoto, Hiroyuki Sakurai, Kenji Matsumoto, Masachika Fujiwara, Koichiro Saito |
Journal | Allergology international : official journal of the Japanese Society of Allergology
(Allergol Int)
Vol. 71
Issue 1
Pg. 83-93
(Jan 2022)
ISSN: 1440-1592 [Electronic] England |
PMID | 34412988
(Publication Type: Journal Article)
|
Copyright | Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved. |
Chemical References |
- RNA, Messenger
- Receptor, Galanin, Type 2
- Galanin
|
Topics |
- Animals
- Disease Models, Animal
- Female
- Galanin
(genetics, metabolism)
- Humans
- Mice
- Mice, Inbred BALB C
- Nasal Mucosa
(metabolism, pathology)
- RNA, Messenger
(metabolism)
- Receptor, Galanin, Type 2
(genetics, metabolism)
- Rhinitis, Allergic
(genetics, metabolism)
- Signal Transduction
|