Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E2
Tóm tắt
Prostaglandin E2 (PGE2), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE2. Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE2 or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE2, PGI2, PGD2 were also determined in bronchoalveolar lavage fluid. HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE2 and PGI2, but not PGD2, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE2 attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE2 and PGI2 production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE2 overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE2, but not in those treated with sulprostone. The lung COX-2/PGE2/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE2 downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE2 to exert its protective effect.
Tài liệu tham khảo
Peters SP, Ferguson G, Deniz Y, Reisner C: Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006, 100 (7): 1139-1151. 10.1016/j.rmed.2006.03.031.
Holgate S, Bisgaard H, Bjermer L, Haahtela T, Haughney J, Horne R, McIvor A, Palkonen S, Price DB, Thomas M, Valovirta E, Wahn U: The Brussels Declaration: the need for change in asthma management. Eur Respir J. 2008, 32 (6): 1433-1442. 10.1183/09031936.00053108.
Finkelman FD, Wills-Karp M: Usefulness and optimization of mouse models of allergic airway disease. J Allrgy Clin Immunol. 2008, 121: 603-606. 10.1016/j.jaci.2008.01.008.
Yang G, Li L, Volk A, Emmell E, Petley T, Giles-Komar J, Rafferty P, Lakshminarayanan M, Griswold DE, Bugelski PJ, Das AM: Therapeutic dosing with anti-interleukin-13 monoclonal antibody inhibits asthma progression in mice. J Pharmacol Exp Ther. 2005, 313 (1): 8-15. 10.1124/jpet.104.076133.
Huang SK, Peters-Golden M: Eicosanoid lipid mediators in fibrotic lung diseases. Chest. 2008, 133 (6): 1442-1450. 10.1378/chest.08-0306.
Gauvreau GM, Watson RM, O'Byrne PM: Protective effects of inhaled PGE2 on allergen-induced airway responses and airway inflammation. Am J Respir Crit Care Med. 1999, 159: 31-36.
Sturm EM, Schratl P, Schuligoi R, Konya V, Sturm GJ, Lippe IT, Peskar BA, Heinemann A: Prostaglandin E2 inhibits eosinophil trafficking through E-prostanoid 2 receptors. J Immunol. 2008, 181 (10): 7273-7283.
Kay LJ, Yeo WW, Peachell PT: Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation. Br J Pharmacol. 2006, 147 (7): 707-713. 10.1038/sj.bjp.0706664.
De Campo BA, Henry PJ: Stimulation of protease-activated receptor-2 inhibits airway eosinophilia, hyperresponsiveness and bronchoconstriction in a murine model of allergic inflammation. Br J Pharmacol. 2005, 144: 1100-1108. 10.1038/sj.bjp.0706150.
Peebles RSJ, Hashimoto K, Morrow JD, Dworski R, Collins RD, Hashimoto Y, Christman JW, Kang KH, Jarzecka K, Furlong J, Mitchell DB, Talati M, Graham BS, Sheller JR: Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice. Am J Respir Crit Care Med. 2002, 165: 1154-1160.
Gavett SH, Madison SL, Chulada PC, Scarborough PE, Qu W, Boyle JE, Tiano HF, Lee CA, Langenbach R, Roggli VL, Zeldin DC: Allergic lung responses are increased in prostaglandin H synthase-deficient mice. J Clin Invest. 1999, 104: 721-732. 10.1172/JCI6890.
Torres R, Herrerias A, Serra M, Roca-Ferrer J, Pujols L, Marco A, Picado C, de Mora F: An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice. Respir Res. 2008, 9 (1): 72-10.1186/1465-9921-9-72.
Torres R, Pérez M, Marco A, Picado C, de Mora F: A cyclooxygenase-2 selective inhibitor, worsens respiratory function and enhances mast cells activity in a murine model of allergic asthma. Arch Bronconeumol. 45 (4): 162-7.
Herrerias A, Torres R, Serra M, Marco A, Roca-Ferrer J, Picado C, de Mora F: Subcutaneous prostaglandin E2 restrains airway mast cell activity in vivo and reduces airway eosinophilia and lung Th2 cytokine overproduction in a house dust mite-induced mouse model of asthma. Int Arch Allergy Immunol. 2009, 149 (4): 323-332. 10.1159/000205578.
Duffy SM, Cruse G, Cockerill SL, Brightling CE, Bradding P: Engagement of the EP2 prostanoid receptor closes the K+ channel KCa3.1 in human lung mast cells and attenuates their migration. Eur J Immunol. 2008, 38 (9): 2548-2556. 10.1002/eji.200738106.
Son Y, Ito T, Ozaki Y, Tanijiri T, Yokoi T, Nakamura K, Takebayashi M, Amakawa R, Fukuhara S: Prostaglandin E2 is a negative regulator on human plasmacytoid dendritic cells. Immunology. 2006, 119 (1): 36-42. 10.1111/j.1365-2567.2006.02402.x.
Okano M, Sugata Y, Fujiwara T, Matsumoto R, Nishibori M, Shimizu K, Maeda M, Kimura Y, Kariya S, Hattori H, Yokoyama M, Kino K, Nishizaki K: E prostanoid 2 (EP2)/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2. Immunology. 2006, 118 (3): 343-352. 10.1111/j.1365-2567.2006.02376.x.
Bonazzi A, Bolla M, Buccellati C, Hernandez A, Zarini S, Viganò T, Fumagalli F, Viappiani S, Ravasi S, Zannini P, Chiesa G, Folco G, Sala A: Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. Am J Respir Crit Care Med. 2000, 162 (6): 2272-2277.
Hinz B, Brune K, Pahl A: Prostaglandin E(2) upregulates cyclooxygenase-2 expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biochem Biophys Res Commun. 2000, 272 (3): 744-748. 10.1006/bbrc.2000.2859.
Lo CJ, Chiu KC, Fu M, Lo R, Helton S: Fish oil augments macrophage cyclooxygenase II (COX-2) gene expression induced by endotoxin. J Surg Res. 1999, 86 (1): 103-107. 10.1006/jsre.1999.5684.
Weinreb M, Machwate M, Shir N, Abramovitz M, Rodan GA, Harada S: Expression of the prostaglandin E(2) (PGE(2)) receptor subtype EP(4) and its regulation by PGE(2) in osteoblastic cell lines and adult rat bone tissue. Bone. 2001, 28 (3): 275-281. 10.1016/S8756-3282(00)00447-6.
Yun SP, Lee MY, Ryu JM, Han HJ: Interaction between PGE2 and EGF receptor through MAPKs in mouse embryonic stem cell proliferation. Cell Mol Life Sci. 2009, 66 (9): 1603-16. 10.1007/s00018-009-9076-8.
Kunikata T, Yamane H, Segi E, Matsuoka T, Sugimoto Y, Tanaka S, Tanaka H, Nagai H, Ichikawa A, Narumiya S: Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat Immunol. 2005, 6 (5): 524-31. 10.1038/ni1188.
Pfaffl MW, Horgan GW, Dempfle L: Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002, 30 (9): e36-10.1093/nar/30.9.e36.
Jaffar Z, Wan KS, Roberts K: A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen. J Immunol. 2002, 169 (10): 5997-6004.
Cipollone F, Cicolini G, Bucci M: Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives. Pharmacol Ther. 2008, 118 (2): 161-180. 10.1016/j.pharmthera.2008.01.002.
Oguma T, Asano K, Shiomi T, Fukunaga K, Suzuki Y, Nakamura M, Matsubara H, Sheldon HK, Haley KJ, Lilly CM, Drazen JM, Yamaguchi K: Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs. Am J Respir Crit Care Med. 2002, 165 (3): 382-386.
Chambers LS, Black JL, Ge Q, Carlin SM, Au WW, Poniris M, Thompson J, Johnson PR, Burgess JK: PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2003, 285: L619-L627.
Picado C, Bioque G, Roca-Ferrer J, Pujols L, Mullol J, Benitez P, Bulbena O: Nuclear factor-kappaB activity is down-regulated in nasal polyps from aspirin-sensitive asthmatics. Allergy. 2003, 58: 122-126. 10.1034/j.1398-9995.2003.23792.x.
Vancheri C, Mastruzzo C, Sortino MA, Crimi N: The lung as a privileged site for the beneficial actions of PGE2. Trends in Immunol. 2004, 25 (1): 40-46. 10.1016/j.it.2003.11.001.
Burgess JK, Ge Q, Boustany S, Black JL, Johnson PR: Increased sensitivity of asthmatic airway smooth muscle cells to prostaglandin E2 might be mediated by increased numbers of E-prostanoid receptors. J Allergy Clin Immunol. 2004, 113 (5): 876-881. 10.1016/j.jaci.2004.02.029.
Oguma T, Asano K, Ishizaka A: Role of Prostaglandin D(2) and its receptors in the pathophysiology of asthma. Allergol Int. 2008, 57 (4): 307-312. 10.2332/allergolint.08-RAI-0033.
Shiraishi Y, Asano K, Nakajima T, Oguma T, Suzuki Y, Shiomi T, Sayama K, Niimi K, Wakaki M, Kagyo J, Ikeda E, Hirai H, Yamaguchi K, Ishizaka A: Prostaglandin D2-induced eosinophilic airway inflammation is mediated by CRTH2 receptor. J Pharmacol Exp Ther. 2005, 312 (3): 954-60. 10.1124/jpet.104.078212.
Profita M, Sala A, Bonanno A, Riccobono L, Siena L, Melis MR, Di Giorgi R, Mirabella F, Gjomarkaj M, Bonsignore G, Vignola AM: Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia. J Allergy Clin Immunol. 2003, 112 (4): 709-716. 10.1016/S0091-6749(03)01889-X.
Pierzchalska M, Szabó Z, Sanak M, Soja J, Szczeklik A: Deficient prostaglandin E2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma. J Allergy Clin Immunol. 2003, 111 (5): 1041-1048. 10.1067/mai.2003.1491.
Wenzel SE, Westcott JY, Smith HR, Larsen GL: Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups. An alteration in the ratio of bronchoconstrictive to bronchoprotective mediators. Am Rev Respir Dis. 1989, 139 (2): 450-457.
Dahlén SE, Hansson G, Hedqvist P, Björck T, Granström E, Dahlén B: Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci USA. 1983, 80 (6): 1712-1716. 10.1073/pnas.80.6.1712.
Pujols L, Mullol J, Alobid I, Roca-Ferrer J, Xaubet A, Picado C: Dynamics of COX-2 in nasal mucosa and nasal polyps from aspirin-tolerant and aspirin-intolerant patients with asthma. J Allergy Clin Immunol. 2004, 114 (4): 814-819. 10.1016/j.jaci.2004.07.050.