Effects of prostaglandin D2, 15-deoxy-Δ12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats

被引:57
作者
Almishri, W
Cossette, C
Rokach, J
Martin, JG
Hamid, Q
Powell, WS
机构
[1] McGill Univ, Meakins Christie Labs, Dept Med, Montreal, PQ H2X 2P2, Canada
[2] Florida Inst Technol, Claude Pepper Inst, Melbourne, FL 32901 USA
[3] Florida Inst Technol, Dept Chem, Melbourne, FL 32901 USA
关键词
D O I
10.1124/jpet.104.079079
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Prostaglandin (PG) D-2 is an arachidonic acid metabolite that is released by allergen-stimulated mast cells. It is a potent in vitro chemoattractant for human eosinophils, acting through the DP2 receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Furthermore, there is in vivo evidence that PGD(2) contributes to allergen-induced pulmonary eosinophilia via its classic DP1 receptor. The PGD(2)-derived product 15-deoxy-Delta(12,14)-PGJ(2) is widely used as a peroxisome proliferator-activated receptor gamma agonist and has been shown to have anti-inflammatory properties. However, this substance can also activate eosinophils in vitro through the DP2 receptor. The objectives of the present study were to determine whether PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) can induce pulmonary eosinophilia, and, if so, to examine the abilities of selective DP1 and DP2 receptor agonists to induce this response. Brown Norway rats were treated by intratracheal instillation of PGs. Vehicle and 5-oxo-6,8,11,14-eicosatetraenoic acid were used as negative and positive controls, respectively. Lung eosinophils were identified by immunostaining of lung sections with an antibody to major basic protein. Both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) induced robust eosinophilic responses that were apparent by 12 h and persisted for at least 48 h. Two selective DP2 receptor agonists, 15R-methyl-PGD(2) and 13-14-dihydro-15-keto-PGD(2), induced similar responses, the former being more potent than PGD(2), whereas the latter was less potent. The selective DP1 receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] was completely inactive. We conclude that PGD(2) and 15-deoxy- Delta(12,14)-PGJ(2) induce eosinophil infiltration into the lungs through the DP2 receptor. The potent in vitro DP2 receptor agonist 15R-methyl-PGD(2) is also very active in vivo and should be a useful tool in examining the role of this receptor.
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页码:64 / 69
页数:6
相关论文
共 37 条
[1]  
Arimura A, 2001, J PHARMACOL EXP THER, V298, P411
[2]   Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the litigation of PPARγ [J].
Bell-Parikh, LC ;
Ide, T ;
Lawson, JA ;
McNamara, P ;
Reilly, M ;
FitzGerald, GA .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (06) :945-955
[3]   International Union of Pharmacology XLIV.: Nomenclature for the oxoeicosanoid receptor [J].
Brink, C ;
Dahlén, SE ;
Drazen, J ;
Evans, JF ;
Hay, DWP ;
Rovati, GE ;
Serhan, CN ;
Shimizu, T ;
Yokomizo, T .
PHARMACOLOGICAL REVIEWS, 2004, 56 (01) :149-157
[4]   PROSTANOID-INDUCED CONTRACTION OF HUMAN BRONCHIAL SMOOTH-MUSCLE IS MEDIATED BY TP-RECEPTORS [J].
COLEMAN, RA ;
SHELDRICK, RLG .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 96 (03) :688-692
[5]   The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 attenuates the development of acute and chronic inflammation [J].
Cuzzocrea, S ;
Wayman, NS ;
Mazzon, E ;
Dugo, L ;
Di Paola, R ;
Serraino, I ;
Britti, D ;
Chatterjee, PK ;
Caputi, AP ;
Thiemermann, C .
MOLECULAR PHARMACOLOGY, 2002, 61 (05) :997-1007
[6]   PROSTAGLANDIN-D2 CAUSES ACCUMULATION OF EOSINOPHILS IN THE LUMEN OF THE DOG TRACHEA [J].
EMERY, DL ;
DJOKIC, TD ;
GRAF, PD ;
NADEL, JA .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 67 (03) :959-962
[7]  
FITZPATRICK FA, 1983, J BIOL CHEM, V258, P1713
[8]  
FLOWER RJ, 1976, BRIT J PHARMACOL, V56, P229, DOI 10.1111/j.1476-5381.1976.tb07446.x
[9]  
FREW AJ, 1988, J IMMUNOL, V141, P4158
[10]   Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice [J].
Fujitani, Y ;
Kanaoka, Y ;
Aritake, K ;
Uodome, N ;
Okazaki-Hatake, K ;
Urade, Y .
JOURNAL OF IMMUNOLOGY, 2002, 168 (01) :443-449