Funding sources The funding was provided by the MRC and the NIHR Biomedical Research Centre Programme and Comprehensive Local Research Network.
CLINICAL AND LABORATORY INVESTIGATIONS
Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes
Version of Record online: 11 JUL 2011
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 165, Issue 3, pages 492–498, September 2011
How to Cite
Gutowska-Owsiak, D., Schaupp, A.L., Salimi, M., Taylor, S. and Ogg, G.S. (2011), Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. British Journal of Dermatology, 165: 492–498. doi: 10.1111/j.1365-2133.2011.10400.x
Conflicts of interest None declared.
- Issue online: 28 AUG 2011
- Version of Record online: 11 JUL 2011
- Accepted manuscript online: 12 MAY 2011 09:42AM EST
- Accepted for publication 20 April 2011
Background The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Interleukin (IL)-22 is upregulated in lesional AE tissue, but its effects on filaggrin expression and genes associated with epidermal function have not yet been comprehensively addressed.
Objectives To investigate the effects of IL-22 on expression of filaggrin and genes encoding proteins relevant to epidermal function.
Methods Microarray analysis was performed on IL-22-stimulated HaCaT keratinocytes. Filaggrin protein level was assessed by an intracellular enzyme-linked immunosorbent assay (ELISA) and Western blot in HaCaT cells and the findings were validated in primary keratinocytes.
Results Exposure to IL-22 cytokine resulted in a downregulation of profilaggrin mRNA expression in HaCaT keratinocytes. The expression of genes involved in enzymatic processing of profilaggrin as well as the generation of natural moisturizing factor was also altered. Furthermore, there was an upregulation of many transcripts encoding proteins of the S100 family. Profilaggrin/filaggrin downregulation was detected by intracellular ELISA and Western blot in HaCaT cells. The relevance to the primary setting was confirmed in primary keratinocytes by Western blot.
Conclusions IL-22 downregulates profilaggrin/filaggrin expression in keratinocytes at both mRNA and protein levels and affects genes relevant to epidermal function. This novel pathway may have relevance to the pathogenesis and treatment of atopic and other skin disease.