The IL-33-induced p38-/JNK1/2-TNF alpha axis is antagonized by activation of beta-adrenergic-receptors in dendritic cells

IL-33, an IL-1 cytokine superfamily member, induces the activation of the canonical NF-kappa B signaling, and of Mitogen Activated Protein Kinases (MAPKs). In dendritic cells (DCs) IL-33 induces the production of IL-6, IL-13 and TNF alpha. Thereby, the production of IL-6 depends on RelA whereas the production of IL-13 depends on the p38-MK2/3 signaling module. Here, we show that in addition to p65 and the p38-MK2/3 signaling module, JNK1/2 are essential for the IL-33-induced TNF alpha production. The central roles of JNK1/2 and p38 in DCs are underpinned by the fact that these two MAPK pathways are controlled by activated beta -adrenergic receptors resulting in a selective regulation of the IL-33-induced TNF alpha response in DCs.