1084 Localization and up-Regulation of CysLT2 Receptor in Perennial Allergic Rhinitis

Friday, 7 December 2012
Hall 4 (HICC)

Hideaki Shirasaki, MD, PhD , Otolaryngology, Sapporo Medical University, Sapporo, Japan

Etsuko Kanaizumi, MD, PhD , Sapporo Medical University, Japan

Nobuhiko Seki, MD, PhD , Sapporo Medical University, Japan

Manabu Fujita, PhD , Minase Research Institute,Ono Pharmaceutical, Japan

Tetsuo Himi, MD, PhD , Sapporo Medical University, Japan

Background: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies using CysLTs indicate two classes of receptors named CysLT1 and CysLT2 receptor exist. The former is sensitive to the CysLT1 receptor antagonists currently used to treat asthma and allergic rhinitis. We have previously reported the localization of CysLT1 receptor by using immunohistochemistry and in situ hybridization. To clarify the expression of CysLT2 receptor in human nasal mucosa, we investigated the expression and the localization of CysLT2 receptor in human nasal mucosa by means of Western blot analysis and immunohistochemistry.

Methods: Human turbinates were obtained by turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. CysLT2 receptor expression on nasal mucosa was studied by Western blot analysis and immunohistochemistry. Also, to investigate the possible modulation of  CysLT2 receptor expression, human umbilical vein endothelial cells (HUVECs) were stimulated with IL-4 or IL-13, and CysLT2 receptor expression were evaluated by Western blot analysis.

Results: About 40kDa band was detected in human turbinates by western blot analysis using anti-CysLT2 receptor antibody. The expression level of CysLT2 receptor protein was marked in patients with nasal allergy than in patients with non-allergic rhinitis. The immunohistochemical study revealed that both vascular endothelial cells and vascular smooth muscles showed intense immunoreactivity for CysLT2 receptor. IL-13 enhanced the levels of CysLT2 receptor protein in HUVECs.

Conclusions: The results suggest a primary role for CysLT2 receptor as the vascular responses in upper respiratory tract,and vascular CysLT2receptor expression can be regulated by Th2 cytokines.