RT Journal Article
SR Electronic
T1 The Interplay Between Innate Immunity (TLR-4) and sCD40L in the Context of an Animal Model of Colitis-associated Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5457
OP 5462
DO 10.21873/anticanres.14556
VO 40
IS 10
A1 ANASTASIOS ANGELOU
A1 APOSTOLOS E. PAPALOIS
A1 EFSTATHIOS ANTONIOU
A1 JAEYUN WANG
A1 NEDA AMINI
A1 ANASTASIA PIKOULI
A1 NIKOLAOS ANDREATOS
A1 STEFAN BUETTNER
A1 MUHAMMAD MUNIR
A1 GEORGIOS THEODOROPOULOS
A1 GEORGIOS C. ZOGRAFOS
A1 PANAGIOTIS SARANTIS
A1 ALESSANDRA PULVIRENTI
A1 CARSTEN KAMPHUES
A1 STAMATIOS THEOCHARIS
A1 EMMANOUIL PIKOULIS
A1 GEORGIOS ANTONIOS MARGONIS
YR 2020
UL http://ar.iiarjournals.org/content/40/10/5457.abstract
AB 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.