GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299040/suppl/GSE299040_Seq_iBMDM.txt.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299040/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299040GEOGSEfalseMK2/p38/p53 negatively regulate basal IL-1β and noncanonical NF-κB signalingInterleukin (IL)-1β is an endogenous pro-inflammatory pyrogen that affects both the innate and adaptive immune systems. Uncontrolled release of IL-1β is associated with sterile inflammatory diseases, such as arthritis, gout, and atherosclerosis as well as the development of tumors. In an initial investigation of the role of the MAPKAP kinase MK2 in IL-1β processing in macrophages, we found that Il1b mRNA and IL-1β protein levels were increased in unstimulated MK2-knockout (KO) macrophages. Additionally, we observed elevated basal IL-1β concentrations in the serum of MK2/3 double KO mice. Further analysis revealed an activation of the noncanonical NF-κB pathway in the absence of MK2 or its interacting activator p38α. Rescue by overexpression of MK2, its kinase-inactive mutant MK2K79R or p38α reduced activation of the noncanonical NF-κB pathway components as well as Il1b mRNA expression. Interestingly, the basal protein level of the tumor suppressor p53 is reduced in the absence of MK2 or p38α.We demonstrate that p53 interacts with mitochondrial caspase-3, which cleaves RelB and therefore inhibits the noncanonical NF-κB pathway, affecting subsequent Il1b and p53 expression. These results not only explain the increased basal levels in MK2-knockout macrophages, but also uncover a new autoregulatory mechanism of p53 expression. Additionally, they reveal a new mechanism that contributes to the long-discussed link between cancer and inflammation, in which the tumor suppressor p53 represses cytokine expression.2026/04/02GSE299040GSM9031214GSM9031217GSM9031215GSM903121621626299040Mus musculus