Interferon-g induces upregulation and activation of the interleukin-31 receptor in human dermal microvascular endothelial cells

Interleukin-31 (IL-31), a recently discovered cytokine derived from T helper cells, is involved in chronic dermatitis and pruritus. This study demonstrates for the first time that the IL-31 receptor complex for IL-31 is substantially upregulated in human dermal microvascular endothelial cells after stimulation with interferon-g (IFN-g). Activation of the IL-31 receptor complex results in the induction of the intracellular ERK1-2 signaling pathway and downregulation of IFN-g-induced monokine induced by IFN-g expression. Inhibitor studies revealed that the IFN-g-induced IL-31RA upregulation is processed via JNK and PI3 kinase activation. In sum, our study points toward an interaction between the TH1-derived cytokine IFN-g and the TH2-derived cytokine IL-31 on endothelial cells.