The interplay between innate immunity (TLR-4) and sCD40L in the context of an animal model of colitis-associated cancer Journal Article

Authors: Angelou, A.; Papalois, A. E.; Antoniou, E.; Wang, J.; Amini, N.; Pikouli, A.; Andreatos, N.; Buettner, S.; Munir, M.; Theodoropoulos, G.; Zografos, G. C.; Sarantis, P.; Pulvirenti, A.; Kamphues, C.; Theocharis, S.; Pikoulis, E.; Margonis, G. A.
Article Title: The interplay between innate immunity (TLR-4) and sCD40L in the context of an animal model of colitis-associated cancer
Abstract: Background/Aim: Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Materials and methods: Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. Results: All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Conclusion: Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer. © 2020 International Institute of Anticancer Research. All rights reserved.
Keywords: genetics; colorectal cancer; mouse; animal; animals; mice; mice, knockout; cd40 ligand; animal model; pathology; carcinogenesis; colorectal neoplasms; disease model; toll like receptor 4; immunology; colorectal tumor; colitis; innate immunity; immunity, innate; disease models, animal; knockout mouse; toll-like receptor 4; tlr4 protein, mouse; dextran sulfate; humans; human; azoxymethane; ibd; aom/dss; colitis associated cancer
Journal Title: Anticancer Research
Volume: 40
Issue: 10
ISSN: 0250-7005
Publisher: International Institute of Anticancer Research  
Date Published: 2020-10-01
Start Page: 5457
End Page: 5462
Language: English
DOI: 10.21873/anticanres.14556
PUBMED: 32988867
PROVIDER: scopus
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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