ORIGINAL PAPER Role of prostaglandin D 2 and E 2 terminal synthases in chronic rhinosinusitis M. Okano à , T. Fujiwara à , M. Yamamoto à , Y. Sugata à , R. Matsumoto à , K. Fukushima à , T. Yoshino w , K. Shimizu z , N. Eguchi ‰ , M. Kiniwa z , Y. Urade ‰ and K. Nishizaki à Departments of à Otolaryngology-Head & Neck Surgery, w Pathology, z Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, ‰ Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan and z Taiho Pharmaceutical Co. Ltd., Saitama, Japan Clinical and Experimental Allergy Correspondence: Mitsuhiro Okano, Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama 700-8558, Japan. E-mail: mokano@cc.okayama-u.ac.jp Summary Background Prostaglandin (PG)D 2 and E 2 , two major cyclooxygenase (COX) products, are generated by PGD 2 synthase (PGDS) and PGE 2 synthase (PGES), respectively, and appear to mediate airway inflammation. Objective We sought to determine the role of PGDS and PGES in the pathophysiology of chronic rhinosinusitis (CRS). Methods The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and five subjects without sinusitis. Immunohistochemistry and quantitative real-time PCR were used to evaluate the expression. Results Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG21 eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non-asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively. Conclusions These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation. Keywords eosinophil, PGD 2 , PGE 2 , sinusitis, synthase Submitted 15 August 2005; revised 14 March 2006; accepted 27 April 2006 Introduction Prostaglandins (PGs) are lipid mediators that regulate immune function [1]. Among these, PGD 2 and PGE 2 are thought to mediate airway inflammation [2]. PGD 2 med- iates a variety of biological activities, including vasodila- tion and bronchoconstriction [3]. Overproduction of PGD 2 induces eosinophilic lung inflammation, and deletion of DP, a PGD 2 receptor, reduces eosinophilic inflam- mation in murine models of asthma [4, 5]. PGE 2 has a pro-inflammatory role by enhancing eosinophil survival and mucin gene expression [6–8]. However, PGE 2 also has anti-inflammatory activity and halts the uncontrolled synthesis and release of cysteinyl leukotrienes from mast cells and inhibits airway smooth muscle cell proliferation [9–12]. Thus, it remains unclear whether PGE 2 are deleter- ious or beneficial in the pathogenesis of airway inflamma- tion. PGD 2 and PGE 2 are derived from arachidonic acid (AA). AA is mobilized from membrane phospholipids by phos- pholipases and is converted to PGH 2 by cyclooxygenase (COX) enzymes. PGH 2 is acted upon by PGD 2 synthase (PGDS) and PGE 2 synthase (PGES) to produce PGD 2 and PGE 2 , respectively [1]. Two distinct types of PGDS exist: lipocalin-type PGDS (l-PGDS) and haemopoietic-type Clinical and Experimental Allergy, 36, 1028–1038  c 2006 The Authors Journal compilation  c 2006 Blackwell Publishing Ltd