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KMID : 0032220200320060481
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Annals of Dermatology
2020 Volume.32 No. 6 p.481 ~ p.486
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Possible Role of Lysine Demethylase 2A in the Pathophysiology of Psoriasis
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Kim Dong-Ha
Choi Mi-Ra
Lee Jae-Kyung
Hong Dong-Kyun
Jung Kyung-Eun
Choi Chong-Won
Lee Young
Kim Chang-Deok
Seo Young-Joon
Lee Jeung-Hoon
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Abstract
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Background: Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed.
Objective: The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis.
Methods: We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model.
Results: Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis.
Conclusion: Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.
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KEYWORD
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Imiquimod, Keratinocytes, Lysine demethylase 2A, Polyinosinic: polycytidylic acid, Psoriasis
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