Ann Dermatol.  2020 Dec;32(6):481-486. 10.5021/ad.2020.32.6.481.

Possible Role of Lysine Demethylase 2A in the Pathophysiology of Psoriasis

• Kim DH
• Choi MR
• Lee JK
• Hong DK
• Jung KE
• Choi CW
• Lee Y
• Kim CD
• Seo YJ
• Lee JH

• KMID: 2508671
• DOI: http://doi.org/10.5021/ad.2020.32.6.481

Abstract

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.

Keyword

Imiquimod; Keratinocytes; Lysine demethylase 2A; Polyinosinic; polycytidylic acid; Psoriasis