Fig. 5

IL-1β-induced Regnase-1 downregulation may produce a variety of cytokines/chemokines important for the intratumor increase in MDSCs. A Relative mRNA levels of Cxcl1, Cxcl2, Csf2, and Tgfb1 in pancreatic tissue of WT mice, pancreas-specific Regnase-1 knockout (PR) mice, pancreas-specific Kras mutant (PK) mice, and pancreas-specific Kras-mutant Regnase-1 knockout (PKR) mice at 24 weeks of age (N = 6 per group). B Relative mRNA levels of Cxcl1, Cxcl2, Csf2, and Tgfb1 in orthotopic syngeneic tumors of WT or Regnase-1 KO pancreatic cancer cells (N = 14–16 per group). C Relative mRNA levels of Cxcl1, Cxcl2, Csf2, and Tgfb1 in WT and Regnase-1 KO murine pancreatic cancer cell lines (N = 3 per group, experiments were performed triplicate). D-E Relative mRNA levels of CXCL1, CXCL2, CSF2, and TGFB1 in human pancreatic cancer cell lines, Panc-1 (D) and MiaPaCa2 (E), upon knockdown (KD) of Regnase-1 by siRNA (N = 3 per group, experiments were performed triplicate). F Regnase-1 and ACTB protein levels in human pancreatic cancer cell lines, Panc-1 (left) and MiaPaCa2 (right), upon knockdown (KD) of Regnase-1 by siRNA. G Heatmap of relative expression levels of representative genes bound to Regnase-1 evaluated by RIP-seq between cells expressing wild-type Regnase-1 or mutant (D141N) Regnase-1 lacking RNase activity. H Relative Il1b mRNA levels in the pancreas of WT mice and pancreatic tumors of pancreas-specific Kras- and Tp53-mutant (KPC) mice (N = 6 per group). I Regnase-1 and ACTB protein levels in human pancreatic cancer cell lines, Panc-1 (left) and MiaPaCa2 (right), with or without IL-1β stimulation. J, K Relative mRNA levels of CXCL1 and CXCL2 in the human pancreatic cancer cell lines Panc-1 (J) and MiaPaCa2 (K) with or without IL-1β stimulation (N = 3 per group, experiments were performed triplicate). Student's t test was used to evaluate differences between 2 groups. One-way ANOVA with Tukey's post hoc test was used to compare differences among 4 groups. *P < 0.05