1. ¹Department of Dermatology, Aarhus Sygehus, Aarhus University Hospital, Aarhus C, Denmark
2. ²Institute of Human Genetics, Aarhus University, Aarhus C, Denmark
3. ³Department of Medical Chemistry, LEO Pharma, Ballerup, Denmark
4. ⁴Institute of Medical Microbiology and Immunology, Aarhus University, Aarhus C, Denmark

Correspondence: Dr Anne T. Funding, Department of Dermatology, Aarhus Sygehus, Aarhus University Hospital, PP Oerumsgade 11, Aarhus C DK-8000, Denmark. E-mail: anne.funding@ki.au.dk

Received 21 September 2005; Revised 4 January 2006; Accepted 19 January 2006; Published online 16 March 2006.

Abstract

Mitogen- and stress-activated protein kinase 1 (MSK1) is a downstream target of both the p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs). MSK1 stimulates transcription of different pro-inflammatory genes through activation of transcription factors. The purpose of this study was to investigate the expression and activation of MSK1 in lesional psoriatic skin and its role in cytokine production in cultured normal human keratinocytes. Western blotting revealed a consistent and significant increase in phosphorylated (activated) MSK1(Ser376) in lesional psoriatic skin. Immunofluorescence staining revealed the phosphorylated MSK1(Thr581) to be localized in the basal layers of the epidermis in lesional psoriatic skin. No staining was found in non-lesional psoriatic skin. Cultured human keratinocytes incubated with anisomycin or IL-1 resulted in the phosphorylation of the p38 MAPK and MSK1(Ser376). MSK1(Ser376) phosphorylation was inhibited by pre-incubation with the p38 inhibitor SB 202190. Transfection of the keratinocytes with specific MSK1 small interfering RNA resulted in 80% reduction of MSK1 expression and 51, 40, and 31% decrease in IL-6, IL-8, and tumor necrosis factor- protein production, respectively. This study demonstrates for the first time the expression of MSK1 in epidermal keratinocytes and increased activation focally in psoriatic epidermis. As MSK1 regulates the production of pro-inflammatory cytokines, it may play a role in the pathogenesis of psoriasis.