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**5** 

*Japan* 

**The Role of Prostanoids in Atopic Dermatitis** 

*Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto* 

Atopic dermatitis (AD) is a common pruritic and chronic inflammatory skin disease, with a prevalence of up to 3% among adults and up to 25% among children (Bieber; Guttman-Yassky et al.; Odhiambo et al., 2009). The clinical features of AD are varied, with patients generally having dry skin, but wet eczematous lesions in the acute stage and lichenification lesions in the chronic stage (Guttman-Yassky et al., 2011). In terms of histology, an increased number of lymphocytes, eosinophils, and mast cells in the dermis are detected. A barrier defect with decreased cornification and epidermal hyperplasia are also characteristic

AD is a multi-factorial disease that arises from complex interaction between genetic and environmental factors. As for its pathogenesis, two models have been proposed: the outside-in model and the inside-out model (Bieber, 2008). In the outside-in model, the decreased skin barrier function caused by genetic defects, such as mutations in filaggrin, allows for the penetration of large immunogenic proteins, which subsequently cause T helper type 2 (Th2) deviated immune activation (Elias et al., 2008; Elias and Schmuth, 2009). In the inside-out model, activation of Th2 cells results in reactive epidermal hyperplasia (Nograles et al.; Ong and Leung, 2006). It has been proposed that the lack of environmental antigens during childhood lead to reduced T helper type 1 (Th1) cellmediated immunity and increased activation of Th2 cells (hygiene hypothesis). In recent reports, involvements of T helper type 17 (Th17) cells and T helper type 22 (Th22) cells

As for the treatment of AD, various therapies have been employed, and the use of topical steroids plays a major role in therapies (Guttman-Yassky et al.). Although the use of topical corticosteroids is the first-line therapy and provides rapid relief of symptoms, prolonged use can cause severe side effects such as skin atrophy. Therefore, alternative therapies with

When tissues are exposed to diverse pathophysiological stimuli, arachidonic acid (AA) is released from membrane phospholipids and converted to lipid mediators, such as prostanoids, leukotrienes (LTs) and hydroxy-eicosatetraenoic acids (HETEs). Prostanoids, including prostaglandins (PG) and thromboxane (TX), are formed by the cyclooxygenase (COX) pathway, whereas LTs and HETEs are formed by the 5-, 12- and 15-lipoxygenase (LO) pathways. COX has two isoforms, COX-1 and COX-2. While COX-1 is constitutively

features of AD (Elias and Schmuth, 2009; Guttman-Yassky et al., 2009).

have also been proposed (Koga et al., 2008; Nograles et al., 2009).

fewer and less extreme side effects are needed.

**2. Characteristics of prostanoids** 

**1. Introduction** 

Tetsuya Honda and Kenji Kabashima

individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk." *J.Allergy Clin.Immunol.* 122(3): 560-568.

