The expression of dual-specificity phosphatase 1 mRNA is downregulated in lesional psoriatic skin

Authors


  • Funding sources
    The Novo Nordic Foundation, the Danish Research Agency, the Lundbeck Foundation, Wyeth, Abbott Laboratories, the Aage Bang Foundation, and the Danish Psoriasis Research Foundation.

  • Conflicts of interests
    None declared.

Lars Iversen.
E-mail: lars.iversen@ki.au.dk

Summary

Background  The p38 mitogen-activated protein kinase (MAPK) plays an important role in inflammatory processes and displays increased activity in psoriasis. Dual-specificity phosphatase 1 (DUSP1) is an important negative regulator of p38 MAPK activity.

Objectives  To study mRNA expression of DUSP1 in normal human epidermal keratinocytes (NHEKs) stimulated with proinflammatory cytokines and to investigate DUSP1 in psoriatic skin.

Methods  NHEKs were cultured in vitro and punch biopsies were obtained from the skin of patients with psoriasis vulgaris and atopic dermatitis. mRNA expression was analysed by reverse transcription–quantitative polymerase chain reaction (RT-qPCR).

Results  In NHEKs, interleukin (IL)-1β induced DUSP1 mRNA expression in a rapid and time-dependent manner through the p38 MAPK/mitogen- and stress-activated kinase (MSK) signalling pathway. DUSP1 mRNA expression was demonstrated to be significantly downregulated in psoriatic skin lesions compared with paired samples of nonlesional psoriatic skin. This was in contrast to atopic dermatitis. The downregulation of DUSP1 mRNA in lesional psoriatic skin was not explained by the difference in the mRNA expression of the potential DUSP1 transcript stability-affecting proteins Hu antigen R or tristetraprolin. Furthermore, DUSP1 mRNA expression was shown not to increase during the early course of treatment with the antitumour necrosis factor-α antibody adalimumab.

Conclusions  In lesional psoriatic skin, the p38 MAPK negative feedback mechanism provided by DUSP1 seems to be inhibited. Downregulation of DUSP1 may contribute to the sustained inflammatory response seen in psoriasis.

Ancillary