Functional effects of interleukin 31 in human primary keratinocytes.
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.
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. kasraie.sadaf@mh-hannover.de
Sadaf
S
Kasraie
M
M
Niebuhr
K
K
Baumert
T
T
Werfel
D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055666:Lipopeptides / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053677:Receptors, Oncostatin M / Q000378:metabolism; D015854:Up-Regulation
C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D055666:Lipopeptides; D018123:Receptors, Interleukin; D053677:Receptors, Oncostatin M; C552442:S-(2,3-bis(palmitoyloxy)propyl)cysteine; D007371:Interferon-gamma