臨床検査51巻5号

2007年05月発行

今月の主題 脂質 脂質関連物質と疾病

プロスタノイドと免疫性皮膚疾患―接触皮膚炎，アトピー性皮膚炎

著者： 椛島健治¹

所属機関： ¹産業医科大学皮膚科学

ページ範囲：P.483 - P.491

　生理活性物質であるプロスタノイドは皮膚の定常状態，あるいは各刺激に伴い合成され，その受容体発現も皮膚に認められている．各プロスタノイドはcontext dependentに，時には互いに相反する作用を発揮し，生体のホメオスタシスの維持や皮膚病態の形成に関与している．プロスタノイドは産生された近傍で作用するオータコイドの一種であるため，副作用の少ない薬物療法につながる可能性が高い．今後はプロスタノイドの病態生理学的役割のさらなる解明とその臨床応用が期待される．〔臨床検査　51：483-491，2007〕

参考文献

1) Narumiya S, Sugimoto Y, Ushikubi F：Prostanoid receptors：structures, properties, and functions. Physiol Rev 79：1193-1226, 1999

2) Leong J, Hughes-Fulford M, Rakhlin N, et al：Cyclooxygenases in human and mouse skin and cultured human keratinocytes：association of COX-2 expression with human keratinocyte differentiation. Exp Cell Res 224：79-87, 1996

3) Torii E, Segi E, Sugimoto Y, et al：Expression of prostaglandin E(2) receptor subtypes in mouse hair follicles. Biochem Biophys Res Commun 290：696-700, 2002

4) Scholz K, Furstenberger G, Muller-Decker K, et al：Differential expression of prostaglandin-H synthase isoenzymes in normal and activated keratinocytes in vivo and in vitro. Biochem J 309：263-269, 1995

5) Rosenbach T, Czernielewski J, Hecker M, et al：Comparison of eicosanoid generation by highly purified human Langerhans cells and keratinocytes. J Invest Dermatol 95：104-107, 1990

6) Hammarstrom S, Lindgren JA, Marcelo C, et al：Arachidonic acid transformations in normal and psoriatic skin. J Invest Dermatol 73：180-183, 1979

7) Ziboh VA, Lord JT, Penneys NS：Alterations of prostaglandin E2-9-ketoreductase activity in proliferating skin. J Lipid Res 18：37-43, 1977

8) Kabashima K, Murata T, Tanaka H, et al：Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity. Nat Immunol 4：694-701, 2003

9) Ruzicka T, Printz MP：Arachidonic acid metabolism in guinea pig skin. Biochim Biophys Acta 711：391-397, 1982

10) Konger RL, Malaviya R, Pentland AP：Growth regulation of primary human keratinocytes by prostaglandin E receptor EP2 and EP3 subtypes. Biochim Biophys Acta 1401：221-234, 1998

11) Tober KL, Wilgus TA, Kusewitt DF, et al：Importance of the EP(1) receptor in cutaneous UVB-induced inflammation and tumor development. J Invest Dermatol 126：205-211, 2006

12) Kabashima K, Miyachi Y：Prostanoids in the cutaneous immune response. J Dermatol Sci 34：177-184, 2004

13) Rocca B, Spain LM, Pure E, et al：Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development. J Clin Invest 103：1469-1477, 1999

14) Nataraj C, Thomas DW, Tilley SL, et al：Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest 108：1229-1235, 2001

15) Tilley SL, Coffman TM, Koller BH：Mixed messages：modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 108：15-23, 2001

16) Fedyk ER, Ripper JM, Brown DM, et al：A molecular analysis of PGE receptor (EP) expression on normal and transformed B lymphocytes：coexpression of EP1, EP2, EP3beta and EP4. Mol Immunol 33：33-45, 1996

17) Fedyk ER, Phipps RP：Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Proc Natl Acad Sci USA 93：10978-10983, 1996

18) Nguyen M, Solle M, Audoly LP, et al：Receptors and signaling mechanisms required for prostaglandin E2-mediated regulation of mast cell degranulation and IL-6 production. J Immunol 169：4586-4593, 2002

19) Mita H, Hasegawa M, Higashi N, et al：Characterization of PGE2 receptor subtypes in human eosinophils. J Allergy Clin Immunol 110：457-459, 2002

20) Peacock CD, Misso NL, Watkins DN, et al：PGE 2 and dibutyryl cyclic adenosine monophosphate prolong eosinophil survival in vitro. J Allergy Clin Immunol 104：153-162, 1999

21) Yamane H, Sugimoto Y, Tanaka S, et al：Prostaglandin E (2) receptors, EP2 and EP4, differentially modulate TNF-alpha and IL-6 production induced by lipopolysaccharide in mouse peritoneal neutrophils. Biochem Biophys Res Commun 278：224-228, 2000

22) Kunikata T, Yamane H, Segi E, et al：Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat Immunol 6：524-531, 2005

23) Becker D, Knop J：Mechanism in allergic contact dermatitis. Exp Dermatol 2：63-69. 1993

24) Grabbe S, Schwarz T：Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today 19：37-44, 1998

25) Homey B, Alenius H, Muller A, et al：CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med 8：157-165, 2002

26) Kabashima K, Sakata D, Nagamachi M, et al：Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells. Nat Med 9：744-749, 2003

27) Angeli V, Faveeuw C, Roye O, et al：Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J Exp Med 193：1135-1147, 2001

28) Takeshita K, Yamasaki T, Nagao K, et al：CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation. Int Immunol 16：947-959, 2004

29) Murakawa M, Yamaoka K, Tanaka Y, et al：Involvement of tumor necrosis factor (TNF)-alpha in phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice. Biochem Pharmacol 71：1331-1336, 2006

30) Kabashima K, Nagamachi M, Honda T, et al：Prostaglandin E(2) is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors. Lab Invest 87：49-55, 2007

31) Laouini D, Elkhal A, Yalcindag A, et al：COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization. J Allergy Clin Immunol 116：390-396, 2005

32) Archer CB, Page CP, Juhlin L, et al：Delayed-onset synergism between leukotriene B4 and prostaglandin E2 in human skin. Prostaglandins 33：799-805, 1987

33) Neisius U, Olsson R, Rukwied R, et al：Prostaglandin E2 induces vasodilation and pruritus, but no protein extravasation in atopic dermatitis and controls. J Am Acad Dermatol 47：28-32, 2002

34) Takahashi Y, Tokuoka S, Masuda T, et al：Augmentation of allergic inflammation in prostanoid IP receptor deficient mice. Br J Pharmacol 137：315-322, 2002

35) Matsuoka T, Hirata M, Tanaka H, et al：Prostaglandin D2 as a mediator of allergic asthma. Science 287：2013-2017, 2000

36) Hirai H, Tanaka K, Yoshie O, et al：Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193：255-261, 2001

37) Yoshimura-Uchiyama C, Iikura M, Yamaguchi M, et al：Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2. Clin Exp Allergy 34：1283-1290, 2004

38) Satoh T, Moroi R, Aritake K, et al：Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. J Immunol 177：2621-2629, 2006

39) Spik I, Brenuchon C, Angeli V, et al：Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J Immunol 174：3703-3708, 2005

40) Iwasaki M, Nagata K, Takano S, et al：Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. J Invest Dermatol 119：609-616, 2002

41) Kanda N, Koike S, Watanabe S：IL-17 suppresses TNF-alpha-induced CCL27 production through induction of COX-2 in human keratinocytes. J Allergy Clin Immunol 116：1144-1150, 2005

42) Kanda N, Koike S, Watanabe S：Prostaglandin E2 enhances neurotrophin-4 production via EP3 receptor in human keratinocytes. J Pharmacol Exp Ther 315：796-804, 2005

43) Arai I, Takano N, Hashimoto Y, et al：Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis. Eur J Pharmacol 505：229-235, 2004