Premium
Functional effects of interleukin 31 in human primary keratinocytes
Author(s) -
Kasraie S.,
Niebuhr M.,
Baumert K.,
Werfel T.
Publication year - 2011
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2011.02545.x
Subject(s) - biology , receptor , interleukin , microbiology and biotechnology , interleukin 4 , keratinocyte , lipoteichoic acid , signal transduction , cytokine , immunology , cell culture , biochemistry , genetics , staphylococcus aureus , bacteria
To cite this article: Kasraie S, Niebuhr M, Baumert K, Werfel T. Functional effects of Interleukin 31 in human primary keratinocytes. Allergy 2011; 66 : 845–852. Abstract Background: Interleukin (IL)‐31 is a T‐cell cytokine acting through a heterodimeric receptor composed of IL‐31RA and OSMR which is expressed on epithelial cells including keratinocytes. A major function of IL‐31 in atopic dermatitis (AD) is the induction of pruritus in the skin. Inflammatory effects of IL‐31 in human primary keratinocytes (HPKs) still remain unclear. We investigated expression, regulation of the IL‐31 receptor as well as functions of IL‐31 in HPKs. Methods: Human primary keratinocytes were stimulated with TLR‐2 ligands (Pam3Cys, lipoteichoic acid and peptidoglycan), or Th1 and Th2 associated cytokines (IFN‐γ and IL‐4), respectively. IL‐31R expression and regulation as well as functional effects of IL‐31 stimulation were then investigated at both the mRNA and protein level and compared with HPKs from patients with AD. The STAT signalling pathway and TLR‐2 expression were investigated using Western blot and Immunohistochemical stainings, respectively. Results: Pam3Cys or IFN‐γ significantly up‐regulated IL‐31RA and OSMR expression. IL‐31 activated STAT‐3 phosphorylation in HPKs which was augmented after preactivation with Pam3Cys or IFN‐γ. IL‐31 enhanced the secretion of CCL2 after up‐regulation of the receptor with Pam3Cys or IFN‐γ. However, this was not observed in keratinocytes from AD patients where an impaired TLR‐2 expression was found. Conclusions: Together, our findings show a functional role of IL‐31 in HPKs and provide a new link between TLR‐2 ligands and IL‐31 which might be dysregulated in AD. Altered function of IL‐31 may have implications for cutaneous inflammation in eczema where skin colonization with Staphylococcus aureus and dysregulation of TLR‐2 have been described.