Figure 3
Blockade of interleukin-1 (IL-1) signaling reduces colitis-associated cancer (CAC) tumorigenesis. (a) Diagram showing the protocols for IL-1R antagonist (IL-1Ra) treatment during CAC induction or during late-stage CAC. Mice were injected intraperitoneally with IL-1Ra (0.5 mg per mouse) or phosphate-buffered saline (PBS) on days 1, 5, and 8 of each dextran sulfate sodium (DSS) cycle or every day after the last DSS cycle (day 84) for 10 days and tumors were examined on day 100. Mice treated during CAC induction were used in b–e. (b) Mice were treated with IL-1Ra or vehicle during CAC induction as shown in a, and then the number of tumors in the colon was counted (left); the right panel shows representative images. (c) The colon tissues were dissected and processed conventionally for hematoxylin and eosin (HE) staining. (d) Colon tissues from mice treated with IL-1Ra or vehicle during CAC induction were isolated and TUNEL (TdT-mediated dNTP nick end labeling) stained (brown) for apoptosis of intestinal epithelial cells (IECs). Six pairs of mice were analyzed. Left: typical result; scale bar=200 μm. The arrows denote the apoptotic cells. Right: summarized results. (e) IECs were isolated from the colons of mice treated with IL-1Ra or vehicle during CAC induction and proteins were extracted, and then phosphorylation of the nuclear factor (NF)-κB p65 subunit and IκBα levels were measured by western blotting. The data shown are representative of those obtained in three independent experiments. **P<0.01; ****P<0.0001.
