Expression and characterization of PGD2 receptors in chronic rhinosinusitis: modulation of DP and CRTH2 by PGD2.
BACKGROUND
Prostaglandin D(2) (PGD(2)) participates in airway inflammation. We reported that levels of hematopoietic-type PGD(2) synthase (h-PGDS) in sinonasal tissues may play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Two PGD(2) receptors have been isolated, DP and CRTH2, but whether they participate in CRS remains unclear. We sought to determine the expression and characterization of DP and CRTH2 in CRS.


METHODS
Expression of DP and CRTH2 in nasal polyps (NP) and uncinate process mucosae (UPM) was examined by in situ hybridization and immunohistochemistry and evaluated by real-time quantitative PCR. h-PGDS, IL-5, eotaxin and RANTES expression was also determined. In addition, the effect of PGD(2) on the expression of both receptors in UPM was assessed.


RESULTS
DP was widely expressed, not only in infiltrating inflammatory cells but also in constitutive cells such as vascular endothelial cells and ciliated columnar epithelia. CRTH2 was selectively expressed in inflammatory cells and some glands. Significantly greater levels of DP mRNA and conversely decreased levels of CRTH2 mRNA were observed in NP compared with UPM. DP and CRTH2 mRNA levels were not only positively and inversely correlated with levels of h-PGDS but also with eotaxin, respectively. Furthermore, addition of PGD(2) significantly increased DP expression and conversely reduced CRTH2 expression in UPM.


CONCLUSIONS
These results suggest that distinct expression of DP and CRTH2 is associated with the pathophysiology of CRS, including NP formation, and the expression of these receptors may be regulated by h-PGDS and PGD(2).
Yamamoto
Miki
M
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Okano
Mitsuhiro
M
Fujiwara
Tazuko
T
Kariya
Shin
S
Higaki
Takaya
T
Nagatsuka
Hitoshi
H
Tsujigiwa
Hidetsugu
H
Yamada
Masao
M
Yoshino
Tadashi
T
Urade
Yoshihiro
Y
Nishizaki
Kazunori
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism / Q000503:physiopathology; D015230:Prostaglandin D2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D012852:Sinusitis / Q000378:metabolism / Q000503:physiopathology*; D055815:Young Adult
D054834:Lipocalins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor