%0 Journal Article
%T IL-1¦Á and IL-1¦Â promote NOD2-induced immune responses by enhancing MAPK signaling
%J -
%D 2019
%R https://doi.org/10.1038/s41374-019-0252-7
%X Both toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) induce a tightly regulated inflammatory response at risk of causing tissue damage, depending on the effectiveness of ensuing negative feedback regulatory mechanisms. Cross-regulation between TLRs, NLRs, and cytokine receptors has been observed. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. In this study, we found that IL-1¦Á/¦Â increased NOD2-induced inflammatory response in human monocytic THP1 cells, peripheral blood mononuclear cells (PBMCs), mouse macrophage RWA264.7 cells and spleen cells, and in an in vivo experiment. IL-1¦Á/¦Â pre-treatment induced the production of CXC chemokines, including growth-regulated oncogene (GRO)-¦Á, GRO-¦Â, and IL-8, and proinflammatory cytokines, including IL-1¦Â, IL-6, and TNF¦Á, which are induced by the activation of NOD2, in a dose- and time-dependent manner. However, pre-treatment with the NOD2 ligand muramyl dipeptide (MDP) did not up-regulate the expression of cytokines induced by IL-1¦Á/¦Â re-treatment. IL-1¦Â treatment increased the expression of A20, which is an important inhibitor of the innate immune response. However, the overexpression of A20 failed to inhibit MDP-induced cytokine production, suggesting that A20 had no effects on the NOD2-induced immune response. In addition, IL-1¦Á/¦Â increased the expression of NOD2 and its downstream adaptor RIP2, and IL-1¦Á/¦Â pre-treatment increased MDP-induced activation of mitogen-activated protein kinases (MAPKs), including ERK, JNK, and P38, which contributed to MDP-induced cytokine production. Based on these results, IL-1¦Á/¦Â promote the NOD2-induced immune responses by enhancing MDP-induced activation of MAPK signaling pathways
%U https://www.nature.com/articles/s41374-019-0252-7