Abstract
Although epidemiologic and experimental evidence strongly indicates chronic inflammation as a risk factor for cancer, it remains unclear how chronic inflammation contributes carcinogenesis. Here we show that deletion of PPARδ diminishes colonic inflammation by reducing infiltration of immune cells via downregulation of pro-inflammatory chemokines and cytokine in a mouse model of colon inflammation. These chemokines are responsible for recruitment of leukocytes from the circulation to local inflammatory sites. Our results further reveal that COX-2 is a downstream target of PPARδ and COX-2-derived PGE2 stimulates macrophages to produce pro-inflammatory chemokines and cytokine. PGE2 is a crucial mediator of colorectal carcinogenesis. More importantly, loss of PPARδ attenuated colonic inflammation-associated adenoma growth in two mouse models of inflammation-associated colorectal cancer. Our results demonstrate that PPARδ promotes chronic colonic inflammation and colitis-associated tumorigenesis. Collectively, these findings indicate that PPARδ plays a pivotal role in connecting colonic inflammation to cancer progression and may represent a potential therapeutic target for prevention or treatment of colorectal cancer.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A43.
- Copyright © American Association for Cancer Research
Volume 4, Issue 10 Supplement
