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Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-?B Mediated Inflammation in Colon Cancer Patients.

ABSTRACT: Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-?B pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-?B. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04-0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074-0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment.

SUBMITTER: Semlali A

PROVIDER: S-EPMC4714746 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients.

Semlali Abdelhabib A Reddy Parine Narasimha N Arafah Maha M Mansour Lamjed L Azzi Arezki A Al Shahrani Omair O Al Amri Abdullah A Shaik Jilani P JP Aljebreen Abdulrahman M AM Alharbi Othman O Almadi Majid A MA Azzam Nahla Ali NA Kohailan Muhammad M Rouabhia Mahmoud M Alanazi Mohammad Saud MS

PloS one 20160115 1

Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-κB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infe ...[more]

PMID: 26771524

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Project description:BackgroundRecent evidence suggests the neurotrophic potential of hepatitis C virus (HCV). HCV NS3 protein is one of the potent antigens of this virus mediating inflammatory response in different cell types. Microglia being the immune surveillance cells in the central nervous system (CNS), the inflammatory potential of NS3 on microglia was studied. Role of toll like receptor (TLR) ligands Pam2CSK3 and Pam3CSK4 in controlling the NS3 mediated microglial inflammation was studied using microglial cell line CHME3.MethodsIL (Interleukin)-8, IL-6, TNF-? (Tumor nicrosis factor alpha) and IL-1? gene expressions were measured by semi quantitative RT-PCR (reverse transcription-PCR). ELISA was performed to detect IL-8, IL-6, TNF-?, IL-1? and IL-10 secretion. FACS (Flourescent activated cell sorting) was performed to quantify TLR1, TLR2, TLR6, MyD88 (Myeloid differntiation factor 88), IkB-? (I kappaB alpha) and pNF-?B (phosphorylated nuclear factor kappaB) expression. Immunofluorescence staining was performed for MyD88, TLR6 and NF-?B (Nuclear factor kappaB). Student's t-test or One way analysis of variance with Bonferoni post hoc test was performed and p < 0.05 was considered significant.ResultsMicroglia responded to NS3 by secreting IL-8, IL-6, TNF-? and IL-1? via TLR2 or TLR6 mediated MyD88/NF-?B pathway. Transcription factor NF-?B was involved in activating the cytokine gene expression and the resultant inflammatory response was controlled by NF-?B inhibitor, Ro106-9920, which is known to down regulate pro-inflammatory cytokine secretion. Activation of the microglia by TLR agonists Pam3CSK4 and Pam2CSK4 induced immune tolerance against NS3. TLR ligand treatment significantly down regulated pro-inflammatory cytokine secretion in the microglia. IL-10 secretion was suggested as the possible mechanism by which TLR agonists induced immune tolerance. NS3 as such was not capable of self-inducing immune tolerance in microglia.ConclusionIn conclusion, NS3 protein was capable of activating microglia and the inflammatory response could be controlled via blocking the transcription factor NF-?B, or by treating the microglia with TLR ligands which likely function via secreting anti-inflammatory cytokines such as IL-10. This can have therapeutic potential in controlling HCV mediated neuroinflammation.

Dataset Information

Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-?B Mediated Inflammation in Colon Cancer Patients.

Publications

Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients.

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