Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease

Background/aim: Interleukin 31 (IL31), primarily expressed in
activated lymphocytes, signals through a heterodimeric receptor
complex consisting of the IL31 receptor alpha (IL31R\textgreeka)
and the oncostatin M receptor (OSMR). The aim of this study was to
analyse IL31 receptor expression, signal transduction, and specific
biological functions of this cytokine system in intestinal
inflammation.Methods: Expression studies were performed by RT-PCR,
quantitative PCR, western blotting, and immunohistochemistry.
Signal transduction was analysed by western blotting. Cell
proliferation was measured by MTS assays, cell migration by
restitution assays.Results: Colorectal cancer derived intestinal
epithelial cell (IEC) lines express both IL31 receptor subunits,
while their expression in unstimulated primary murine IEC was low.
LPS and the proinflammatory cytokines TNF-\textgreeka,
IL1\textgreekb, IFN-\textgreekg, and sodium butyrate stimulation
increased IL31, IL31R\textgreeka, and OSMR mRNA expression, while
IL31 itself enhanced IL8 expression in IEC. IL31 mediates ERK-1/2,
Akt, STAT1, and STAT3 activation in IEC resulting in enhanced IEC
migration. However, at low cell density, IL31 had significant
antiproliferative capacities (p