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Upregulation of TLRs and IL-6 as a marker in human colorectal cancer.

Lu CC, Kuo HC, Wang FS, Jou MH, Lee KC, Chuang JH - Int J Mol Sci (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. cclu999@gmail.com.

ABSTRACT
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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IL-8 expression level of COLO 205 and DLD-1 cell during 3M002 treatment (*p < 0.05).
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ijms-16-00159-f006: IL-8 expression level of COLO 205 and DLD-1 cell during 3M002 treatment (*p < 0.05).

Mentions: The IL-8 expression level of the human colon cancer cell (COLO 205 and DLD-1) were inhibited during 3M002 treatment at 24 and 48 h (p < 0.05) (Figure 6). A similar result was obtained from the human colorectal carcinoma cell in which the IL-6 expression level of the 3M002-treated cell was higher than that in the untreated cell (data not shown). In addition, the Boyden chamber assay was used to evaluate the in vitro migration and invasion effects of 3M002 on DLD-1 cells’ invasiveness. The observations revealed that 3M002 resulted in a remarkable inhibition of CRC cell migration as compared to either treatment alone (Figure 7).


Upregulation of TLRs and IL-6 as a marker in human colorectal cancer.

Lu CC, Kuo HC, Wang FS, Jou MH, Lee KC, Chuang JH - Int J Mol Sci (2014)

IL-8 expression level of COLO 205 and DLD-1 cell during 3M002 treatment (*p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307241&req=5

ijms-16-00159-f006: IL-8 expression level of COLO 205 and DLD-1 cell during 3M002 treatment (*p < 0.05).
Mentions: The IL-8 expression level of the human colon cancer cell (COLO 205 and DLD-1) were inhibited during 3M002 treatment at 24 and 48 h (p < 0.05) (Figure 6). A similar result was obtained from the human colorectal carcinoma cell in which the IL-6 expression level of the 3M002-treated cell was higher than that in the untreated cell (data not shown). In addition, the Boyden chamber assay was used to evaluate the in vitro migration and invasion effects of 3M002 on DLD-1 cells’ invasiveness. The observations revealed that 3M002 resulted in a remarkable inhibition of CRC cell migration as compared to either treatment alone (Figure 7).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. cclu999@gmail.com.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus