Chronic Inflammation and Carcinogenesis

Durum, Scott

Abstract

The new Cancer Inflammation Program has inspired two new projects in colon cancer that diverge from our previous focus on IL-7. One project involves IL-17A , IL-17 F and IL-25. These are T cell cytokines that are produced by cells that strongly promote the intestinal inflammation that leads to colon cancer. It has not been determined where IL-17 and 25 are produced during this inflammatory response. We have developed knockin reporter mice for the two IL-17 genes using two colors and for IL-25. This will enable us to visualize cells producing these critical inflammatory cytokines during bowel inflammation leading to colon cancer. A second project aims to inhibit the bowel inflammation leading to colon cancer. IL-27 and IL-35 are suppressive cytokines that we have cloned into the food bacterium, Lactococcus lactis. These engineered bacteria will be given orally to mice to try to inhibit bowel inflammation leading to colon cancer.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIABC011150-01
• Application #: 7966115
• Support Year: 1
• Fiscal Year: 2009
• Total Cost: $419,748

Institution

• Name: National Cancer Institute Division of Basic Sciences

Publications

Aiello, Francesca B; Guszczynski, Tad; Li, Wenqing et al. (2018) IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal 47:131-141

Senkevitch, Emilee; Li, Wenqing; Hixon, Julie A et al. (2018) Inhibiting Janus Kinase 1 and BCL-2 to treat T cell acute lymphoblastic leukemia with IL7-R? mutations. Oncotarget 9:22605-22617

Francois, Bruno; Jeannet, Robin; Daix, Thomas et al. (2018) Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight 3:

Andrews, Caroline; McLean, Mairi H; Durum, Scott K (2018) Cytokine Tuning of Intestinal Epithelial Function. Front Immunol 9:1270

Cramer, Sarah D; Hixon, Julie A; Andrews, Caroline et al. (2018) Mutant IL-7R? and mutant NRas are sufficient to induce murine T cell acute lymphoblastic leukemia. Leukemia 32:1795-1882

Yoshimura, Teizo; McLean, Mairi H; Dzutsev, Amiran K et al. (2018) The Antimicrobial Peptide CRAMP Is Essential for Colon Homeostasis by Maintaining Microbiota Balance. J Immunol 200:2174-2185

Rodriguez-Palacios, Alexander; Harding, Andrew; Menghini, Paola et al. (2018) The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn's Disease-Like Ileitis. Inflamm Bowel Dis 24:1005-1020

Porter, Ross John; Andrews, Caroline; Brice, Daniel Paul et al. (2018) Can We Target Endogenous Anti-inflammatory Responses as a Therapeutic Strategy for Inflammatory Bowel Disease? Inflamm Bowel Dis :

Shen, Wei; Li, Wenqing; Hixon, Julie A et al. (2017) Visualization of IL-22-expressing Lymphocytes Using Reporter Mice. J Vis Exp :

McLean, Mairi H; Andrews, Caroline; Hanson, Miranda L et al. (2017) Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through Interleukin-10-Dependent, T-Cell-Independent Attenuation of Colonic Mucosal Innate Immune Responses. Inflamm Bowel Dis 23:1983-1995