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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...

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Autores principales: Lu, Chien-Chang, Kuo, Hsing-Chun, Wang, Feng-Sheng, Jou, Ming-Huey, Lee, Ko-Chao, Chuang, Jiin-Haur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
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.
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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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