TGF-beta signaling may play a role in the development of goblet cell hyperplasia in a mouse model of allergic rhinitis

• Published in: Allergology international Vol. 59; no. 3; pp. 313 - 319
• Main Authors: Ouyang, Yuhui, Miyata, Masanori, Hatsushika, Kyosuke, Ohnuma, Yuko, Katoh, Ryohei, Ogawa, Hideoki, Okumura, Ko, Masuyama, Keisuke, Nakao, Atsuhito
• Format: Journal Article
• Language: English
• Published: England Elsevier 2010
• Subjects: Animals; Cell Proliferation - drug effects; Disease Models, Animal; Goblet Cells - drug effects; Goblet Cells - immunology; Goblet Cells - metabolism; Goblet Cells - pathology; Humans; Hyperplasia; Immunization; Mice; Nasal Mucosa - drug effects; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Ovalbumin - administration & dosage; Ovalbumin - immunology; Phosphorylation; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Pyrazoles - pharmacology; Quinolines - pharmacology; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; Rhinitis, Allergic, Perennial - immunology; Rhinitis, Allergic, Perennial - metabolism; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - metabolism; Signal Transduction - drug effects; Smad2 Protein - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism
• ISSN: 1323-8930; 1440-1592
• DOI: 10.2332/allergolint.10-SC-0172

Transforming growth factor-beta (TGF-beta) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-beta is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-beta expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-beta signaling is activated in allergic rhinitis and plays a role in the pathophysiology of allergic rhinitis. An ovabumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis was established and phosphorylation of Smad2 in the nasal mucosa was examined by immunohistochemistry. In addition, the effects of the pharmacological inhibition of endogenous TGF-beta signaling on the allergic rhinitis model were histologically examined. Furthermore, phosphorylation of Smad2 in the nasal mucosa samples obtained from patients with allergic rhinitis was also evaluated. In the mouse model of allergic rhinitis, OVA challenge induced phosphorylation of Smad2 predominantly in epithelial cells in the nasal mucosa. In addition, the administration of an inhibitor of TGF-beta type I receptor kinase activity during OVA challenge suppressed goblet cell hyperplasia in the nasal mucosa. Furthermore, phosphorylated Smad2 expression increased in nasal epithelial cells in patients with allergic rhinitis. These results suggest that TGF-beta signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia.