Expression of cysLT1 and cysLT2 Receptor in Chronic Hyperplastic Eosinophilic Sinusitis

Abstract

Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS.

Practical Medical and Surgical Management of Chronic Rhinosinusitis

“…In NES, there is no upregulation for genes associated with IL-4 and IL-13, two cytokines that are associated with eosinophilic allergic infl ammation [ 152 ]. NES has also been shown to be associated with decreased expression of cysLT2R protein [ 174 ], but some studies report that cysLT levels in NES sinonasal mucosa are similar to controls [ 125 ]. NES has also been shown to be associated with decreased expression of cysLT2R protein [ 174 ], but some studies report that cysLT levels in NES sinonasal mucosa are similar to controls [ 125 ].…”

“…CysLTs are lipid mediators that not only stimulate potent contractive activity of bronchial smooth muscle but also exert proinfl ammatory actions both in the upper and lower airways [ 174 ]. They act on target organs through specifi c receptors [ 174 ], and they are overexpressed in AERD [ 225 , 226 ]. This correlates with the increased number of sinus mucosa infi ltrated eosinophils observed in AERD [ 174 ].…”

“…They act on target organs through specifi c receptors [ 174 ], and they are overexpressed in AERD [ 225 , 226 ]. This correlates with the increased number of sinus mucosa infi ltrated eosinophils observed in AERD [ 174 ]. Sinonasal tissue in AERD also demonstrates upregulation of 5-lipoxygenase and leukotriene C4 synthase [ 163 , 221 , 227 ].…”