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Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer
Toll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal can...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307241/ https://www.ncbi.nlm.nih.gov/pubmed/25547486 http://dx.doi.org/10.3390/ijms16010159 |
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author | Lu, Chien-Chang Kuo, Hsing-Chun Wang, Feng-Sheng Jou, Ming-Huey Lee, Ko-Chao Chuang, Jiin-Haur |
author_facet | Lu, Chien-Chang Kuo, Hsing-Chun Wang, Feng-Sheng Jou, Ming-Huey Lee, Ko-Chao Chuang, Jiin-Haur |
author_sort | Lu, Chien-Chang |
collection | PubMed |
description | Toll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal cancer (CRC) patients. We identified Toll-like receptor 1 (TLR1), TLR2, TLR4 and TLR8 gene expression levels and downstream gene, i.e., interleukin-6 (IL-6), IL-8, interferon-α (IFN-α) and myeloid differentiation primary-response protein-88 (MyD88), expression levels in CRC patients and in cancer cell lines. CRC tissues have higher TLR1, TLR2, TLR4, TLR8, IL-6 and IL-8 gene expression levels than do the normal colon mucosa (p < 0.05). TLR2 expression varied in different cell types (mucosa and lymphocytes). There was no difference in the MyD88 and IFN-α gene expression levels between cancerous and normal colon mucosa. CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence. CL075 (3M002) treatments can reduce the production of IL-8 in different cancer cell lines. The signaling pathway of TLRs in cancer tissue is different from that in normal cells; and is MyD88-independent. Higher expression levels of TLR1, TLR2, TLR 4 and TLR 8 mRNA were related to upregulation inflammatory cytokines IL-6 and IL-8 gene expression in tissue and to the upregulation of IL-6 in blood. The concentration of IL-6 in serum can be used as an indicator of the possibility of CRC recurrence. Treatment with 3M002 can reduce IL-6 production in vitro and may prevent CRC recurrence. Our findings provide evidence that TLR1, TLR2, TLR4 and TLR8 gene expression induce downstream IL-6 and IL-8 gene expression; detection of these expression levels can serve as a CRC marker. |
format | Online Article Text |
id | pubmed-4307241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43072412015-02-02 Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer Lu, Chien-Chang Kuo, Hsing-Chun Wang, Feng-Sheng Jou, Ming-Huey Lee, Ko-Chao Chuang, Jiin-Haur Int J Mol Sci Article Toll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal cancer (CRC) patients. We identified Toll-like receptor 1 (TLR1), TLR2, TLR4 and TLR8 gene expression levels and downstream gene, i.e., interleukin-6 (IL-6), IL-8, interferon-α (IFN-α) and myeloid differentiation primary-response protein-88 (MyD88), expression levels in CRC patients and in cancer cell lines. CRC tissues have higher TLR1, TLR2, TLR4, TLR8, IL-6 and IL-8 gene expression levels than do the normal colon mucosa (p < 0.05). TLR2 expression varied in different cell types (mucosa and lymphocytes). There was no difference in the MyD88 and IFN-α gene expression levels between cancerous and normal colon mucosa. CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence. CL075 (3M002) treatments can reduce the production of IL-8 in different cancer cell lines. The signaling pathway of TLRs in cancer tissue is different from that in normal cells; and is MyD88-independent. Higher expression levels of TLR1, TLR2, TLR 4 and TLR 8 mRNA were related to upregulation inflammatory cytokines IL-6 and IL-8 gene expression in tissue and to the upregulation of IL-6 in blood. The concentration of IL-6 in serum can be used as an indicator of the possibility of CRC recurrence. Treatment with 3M002 can reduce IL-6 production in vitro and may prevent CRC recurrence. Our findings provide evidence that TLR1, TLR2, TLR4 and TLR8 gene expression induce downstream IL-6 and IL-8 gene expression; detection of these expression levels can serve as a CRC marker. MDPI 2014-12-24 /pmc/articles/PMC4307241/ /pubmed/25547486 http://dx.doi.org/10.3390/ijms16010159 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lu, Chien-Chang Kuo, Hsing-Chun Wang, Feng-Sheng Jou, Ming-Huey Lee, Ko-Chao Chuang, Jiin-Haur Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title | Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title_full | Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title_fullStr | Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title_full_unstemmed | Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title_short | Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer |
title_sort | upregulation of tlrs and il-6 as a marker in human colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307241/ https://www.ncbi.nlm.nih.gov/pubmed/25547486 http://dx.doi.org/10.3390/ijms16010159 |
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