Table 1 Indications of PUVA Therapy Psoriasis; psoriasis vulgaris pustular psoriasis psoriatic erythroderma Pustulosis palmaris et plantaris Vitiligo

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1 Table 1 Indications of PUVA Therapy Psoriasis; psoriasis vulgaris pustular psoriasis psoriatic erythroderma Pustulosis palmaris et plantaris Vitiligo vulgaris Takeshi HORIO,M.D., Hiroyuki OKAMOTO,M.D., Hiroko HASHIMOTO,M.D., Miki MISHIMA,M.D. and Mitsuo YAMAWAKI,M.D. Mycosis Sezary Parapsoriasis Atopic Lichen Alopecia Urticaria Solar fungoides syndrome dermatitis planus areata urticaria en plaque pigmentosa Polymorphous light eruption

2 Fig. 1 LC Stained with ATPase in Nontreated(up) PUVA-treated(bottom) Skin of Guinea Pig and

3 Fig. 2 UV-induced Local Immunosuppression Fig. 3 UV-induced Systemic Immunosuppression Fig. 4 Possible Mechanism of UV-induced Tolerance

4

5 Table 2 Keratinocyte-Derived Cytokines Which are Upregulated by UVB Radiation 1. Musajo L, Rodighiero G, Dall'Acqua F: Evidences of a photoreaction of the photosensitizing furocoumarins with DNA and with pyrimidinc nucico- sides and nucleotides, Experientia, 21:24-25, Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA: Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light, N Engl J Med, 291: , Morison WL, Parrish JA, Fitzpartrick TB: Oral psoralen photochemotherapy of atopic eczema. Br J Dermatol, 98:25-32, Okamoto H, Horio T: The effect of 8-methoxypsoralen and long-wave ultraviolet light on Langer- hans cell, J Invest Dermatol, 77: , Horio T, Okamoto H: The mechanisms of inhibi-

6 tory effect of 8-methoxypsoralen and long-wave ultraviolet light on experimental contact sensitization, J Invest Dermatol, 78: , Horio T, Okamoto H: Immunologic unresponsiveness induced by topical application of hapten to PUVA-treated skin in guinea pigs, J Invest Dermatol, 80:90-93, Miyauchi H, Horio T: Ultraviolet B-iuduced local immunosuppression of contact hypersensitivity is modulated by ultraviolet irradiation and hapten application, J Invest Dermatol, 104: , Ullrich SE: Does exposure to UV radiaion induce a shift to a Th-2-like immune reaction?, Photochem Photobiol, 64: , Hammerberg CN, Duraiswamy N, Cooper KD: Active induction of unresponsiveness (tolerace) to DNFB by in vivo ultraviolet-exposed epidermal cells is dependent upon infiltrating class II MHC CD11b monocytic/macrophagic cells, J Immunol, 153: , Streilein JW: Sunlight and skin-associated lymphoid tissues (SALT): If UVB is the trigger and TNF a is its mediator, what is the message?, J Invest Dermatol, 100:47S-52S, Chung HT, Burnham DK, Robertson B, Roberts LK, Daynes RA: Involvement of prostaglandins in the immune alterations caused by the exposure of mice to ultraviolet radiation. J Immunol, 137: , Vink AA, Yarosh DB Kripke ML: Chromophore for UV-induced immunosuppression: DNA, Photochem Photobiol, 63: , Norval M: Chromophore for UV-induced immun osuppression: urocanic acid, Photochem Photobiol, 63: , Morison WL, Parrish JA, Block KJ, Krugler JI: In vivo effect of UVB on lymphocyte function, Br J Dermatol, 101: , Morison WL, Parrish JA, Block KJ, Krugler JI: In vivo effect of PUVA on lymphocyte function, Br J Dermatol, 104: , Okamoto H, Horio T, Maeda M: Alteration of lymphocyte functions by 8-methoxypsoralen and lon g-wave ultraviolet light radiation. II. The effect of in vivo PUVA on IL-2 production, J Invest Dermatol, 89:24-26, Okamoto H, Takigawa M, Horio T: Alteration of lymphocyte functions by 8-methoxypsoralen and long-wave ultraviolet light radiation, Suppressive effect of PUVA on T-lymphocyte migration in vitro, J Invest Dermatol, 84: , Yoshimura M, Inoue Y, Yamawaki M, Horio T: In vitro radiation modulates the expression of CD45 isoforms on human peripheral T cell, J Dermatol Sci, 10:68, Danno K, Toda K, Horio T: The effect of 8- methoxypsoralen and long-wave ultraviolet (PUVA) radiation on mast cells: PUVA suppresses degranulation of mouse skin mast cells induced by compound 48/80, J Invest Dermatol, 85: , Danno K, Toda K, Horio T: Ultraviolet B radiation suppresses mast cell degranulation induced by compound 48/80, J Invest Dermatol, 87: , Toda K, Danno K, Tachibana T, Horio T: Effect of 8-methoxypsoralen plus longwave ultraviolet (PUVA) radiation on mast cells. II. In vitro PUVA inhibits degranulation of rat peritoneal mast cells induced by compound 48/80, J Invest Dermatol, 87: , Danno K, Fujii K, Tachibana T, Toda K, Horio T: Suppressed histamine release from rat peritoneal mast cells by ultraviolet B irradition: decreased diacylglycerol formation as a possible mechanism. J Invest Dermatol, 90: , Norris DA, Lyons MB, Middleton MH, Yohn JJ, Kashihara-Sawami M: Ultraviolet radiation can either suppress or induce expression of intercellular adhesion molecule 1 (ICAM-1) on the surface of cultured human keratinocyte, J Invest Dermatol, 95: , Yamawaki M, Futamura S, Horio T: UVB radiation suppresses the TNF-ƒ -induced expression of E-selectin and ICAM-1 on cultured human umbilical vein endothelial cells, J Dermatol Sci, 13:11-17, 1996

7 25. Yoshimura M, Namura S, Akamatsu H, Horio T: Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro, Br J Dermatol 135: , 1996 The Action Mechanism of Phototherapy with Emphasis on Photoimmunologic Effects Takeshi Horio, Hiroyuki Okamoto, Hiroko Hashimoto, Miki Mishima and Mitsuo Yamawaki Department of Dermatology, Kansai Medical University 10-15, Fumizono, Moriguchi, Osaka 570, Japan Kiichiro Danno Department of Dermatology, Shiga University of Medical Science Seta, Otsu, Shiga , Japan Key words: phototherapy, PUVA therapy, immunecompetent cell, photoimmunology, cytokine Recently phototherapy, including UVB and PUVA, is one of the most popular modalities for the treatment of a variety of cutaneous diseases, although the action mechanisms have not been fully understood. On the other hand, it has been clarified that the skin is an important immunologic organ whose constitutive cells are all involved in immunologic reactions. We have investigated so far the effect of PUVA and UVB radiation on the immunecompetent cells, including epidermal Langerhans cells, T lymphocytes, mast cells and endothelial cells and also on the contact hypersensitivity. The results obtained from these experiments suggest that phototherapy exerts its anti-allergic and anti-inflammatory effects through the immunosuppressive ability. Skin Research, 39: , 1997

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