Inflammation, cytokines, the IL-17/IL-6/STAT3/NF-κB axis, and tumorigenesis

• Main Authors: Chen XW, Zhou SF
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-06-01
• Series: Drug Design, Development and Therapy
• Online Access: http://www.dovepress.com/inflammation-cytokines-the-il-17il-6stat3nf-kappab-axis-and-tumorigene-peer-reviewed-article-DDDT

Xiao-Wu Chen,1 Shu-Feng Zhou2 1Department of General Surgery, The First People’s Hospital of Shunde, Southern Medical University, Shunde, Foshan, Guangdong, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USAIn the recently published paper by Xie et al1 in the journal of Drug Design, Development and Therapy, the authors have evaluated interleukin (IL)-17–driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human benign colon polyps. The authors have observed that human colon adenocarcinomas contained the highest levels of IL-17, which was significantly higher than the IL-17 level in the adenomas, ulcerative colitis, and normal colon tissues (P<0.01). The levels of IL-17 receptor A (IL-17RA) were also the highest in human colon adenocarcinomas, followed by adenomas and ulcerative colitis. The increased level of IL-17 and IL-17RA was accompanied with increased IL-17–driven inflammatory responses, including activation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase pathways, increased expression of matrix metalloproteinase (MMP)-9, MMP-7, MMP-2, B-cell lymphoma, and cyclin D1, decreased expression of Bcl-2-associated X protein, and increased expression of vascular endothelial growth factor (VEGF) and VEGF receptor expression that were associated with increased angiogenesis.1 These data suggest that IL-17–driven inflammatory responses contribute to the initiation, growth, development, and metastasis of colon cancer. IL-17 and its related signaling pathways may serve as promising novel targets in the development of drugs for the prevention and treatment of colon cancer.