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Increased NFκ-B Activity in HCT116 Colorectal Cancer Cell Line Harboring TLR4 Asp299Gly Variant

Davoodi, H. and Hashemi, S.R. and Seow, H.F. (2012) Increased NFκ-B Activity in HCT116 Colorectal Cancer Cell Line Harboring TLR4 Asp299Gly Variant. Iranian Journal of Allergy, Asthma and Immunology, 11 (2). pp. 121-132. ISSN 17351502 (ISSN)

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Abstract

Toll-Like Receptor 4 (TLR4), considered one of the most important TLR, recognizes lipopolysaccharide of gram-negative bacteria. Recognition of ligands by TLRs induces signaling pathways resulting in activation of transcriptional factors such as NF-κB which are involved in the expression of inflammatory cytokines and chemokines. To prevent an inappropriate immune response, a complex network of molecules negatively regulates TLRs and their associated signaling pathways. Two cosegregating single nucleotide polymorphisms of the human TLR4 gene, namely Asp299Gly and Thr399Ile, have been associated with hyporesponsiveness to inhaled LPS. The purpose of this study was to determine the impact of TLR4 gene variant on NF-κB activity in colorectal cancer cell line. HCT116 cells were transfected with wild-type and mutants Flag-CMV1-TLR4 expression vectors. Western blot analysis was performed to evaluate selected molecules involved in TLR4 signaling. NF-κB activity was assessed by dualluciferase reporter assay and cytokine profiles were evaluated by ELISA and Cytometric Bead Array method. Results showed that the activity of pNF-κB was higher in cells harboring TLR4 D299G compared to the other cells. However, the activity of pAKT, pERK1 and pIRAK was higher in wild-type. The results of cytokine measurements showed about four fold higher level of IL-8 in cells with wild-type TLR4. This study suggest that TLR4 Asp299Gly gene variant has an impact on TLR4 signaling and potentially on intestinal homeostasis due to impaired control signals at the epithelial cell level which may lead to chronic intestinal inflammation and interrupted intestinal homeostasis and may eventually lead to colorectal cancer. Copyright© 2012, Iranian Journal of Allergy, Asthma and Immunology. All rights reserved.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Iran. J. Allergy Asthma Immunol. [Field not mapped to EPrints] C2 - 22761186 [Field not mapped to EPrints] AD - Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Faculty of Animal Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran [Field not mapped to EPrints] AD - Department of Pathology, Immunology Unit, Universiti Putra Malaysia, 43400 Serdang Selangor, Malaysia [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: Colorectal cancer, Polymorphism, Toll like receptors, immunoglobulin enhancer binding protein, interleukin 1 receptor associated kinase, interleukin 8, mitogen activated protein kinase 1, protein kinase B, signal transducing adaptor protein, toll like receptor 4, aspartic acid, cytokine, glycine, I kappa B, immunoglobulin enhancer binding protein, interleukin 1 receptor associated kinase, isoprotein, lipopolysaccharide, luciferase, mitogen activated protein kinase 3, protein kinase B, TLR4 protein, human, article, cancer cell culture, cell assay, cell level, cell strain HCT116, colorectal cancer, controlled study, enteritis, enzyme linked immunosorbent assay, expression vector, genetic association, genetic transfection, genetic variability, homeostasis, human, human cell, intestine epithelium cell, protein function, protein phosphorylation, Western blotting, drug effect, flow cytometry, genetics, metabolism, phosphorylation, reporter gene, signal transduction, single nucleotide polymorphism, time, upregulation, Aspartic Acid, Blotting, Western, Cytokines, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genes, Reporter, Glycine, HCT116 Cells, Humans, I-kappa B Proteins, Interleukin-1 Receptor-Associated Kinases, Lipopolysaccharides, Luciferases, Mitogen-Activated Protein Kinase 3, NF-kappa B, Phosphorylation, Polymorphism, Single Nucleotide, Protein Isoforms, Proto-Oncogene Proteins c-akt, Signal Transduction, Time Factors, Toll-Like Receptor 4, Transfection, Up-Regulation
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 18 Apr 2015 05:38
Last Modified: 11 May 2015 07:54
URI: http://eprints.goums.ac.ir/id/eprint/2000

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