The role of cysteinyl leukotrienes and their receptors in refractory nasal polyps

• Published in: Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2017-11, Vol.126, p.39-48
• Main Authors: Du, Jintao, Ba, Luo, Zhou, Jiao, Yu, Lingyu, Liu, Ruowu, Zhang, Jie, Liu, Feng, Xian, Junming, Liu, Shixi, Liu, Yafeng
• Format: Article
• Language: English
• Subjects: Acetates - administration & dosage; Adult; Chronic rhinosinusitis with nasal polyps; Cysteine - genetics; Cysteinyl leukotriene; Cytokines - genetics; Enterotoxins - administration & dosage; Female; Functional endoscopic sinus surgery; Gene Expression Regulation - drug effects; Humans; Leukotriene Antagonists - administration & dosage; Leukotriene receptor antagonist; Leukotrienes - genetics; Male; Middle Aged; Nasal Polyps - drug therapy; Nasal Polyps - genetics; Nasal Polyps - pathology; Quinolines - administration & dosage; Receptors, Leukotriene - genetics; Sinusitis - drug therapy; Sinusitis - genetics; Sinusitis - pathology; Type 1 cysteinyl leukotriene receptors
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2017.09.009

Leukotriene signaling is essential in many diseases, including asthma, allergic rhinitis, atherosclerosis and inflammatory bowel disease. Nevertheless, the expression of cysteinyl leukotrienes (CysLTs) and its receptors (CYSLTRs) in different types of nasal polyps (NPs), and the role of their antagonist in the treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) are not well understood. The following study investigates the expression of CysLTs and CYSLTRs in different types of NPs, as well as the role of leukotriene receptor antagonist (montelukast) in refractory NPs. Our data showed that CysLTs and CYSLTRs were significantly elevated in CRSwNP group (p < 0.05), particularly in IL-5+NP patients, compared to patients with chronic rhinosinusitis but without NPs (CRSsNP) and the control group. Furthermore, montelukast have shown the ability to inhibit the expression of MUC5AC, TSLP, IL-4, IL-5, IL-13, and TGF-β in NP explants after treatment with Staphylococcal Enterotoxins B (SEB). In addition, the patients treated by additional montelukast have better outcomes compared to those with INCS only. To conclude, our results demonstrate that the inhibition of CysLTs signaling by montelukast decreases the expression of cytokines and mucin in polyp explants, and in turn promotes the recovery in patients with refractory CRSwNP. •The primary types of NPs based on the cytokine patterns of NPs were KCN NPs and IL-5+ NPs.•The expression of CysLTs and its receptors was elevated in nasal polyps, especially in IL-5+ NP patients.•Montelukast, a CYSLTR1 antagonist, inhibited cytokine release in explants following the stimulation of SEB.•Montelukast shortens the recovery course after FESS for refractory patients.