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Increased expression of Toll-like receptors 4 and 9 in human lung cancer

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Abstract

Background It has been reported lately that Toll-like receptors (TLRs) play an essential role in the activation of innate immunity, and TLRs are expressed in a large number of immune cells like B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells as well as epithelial cells. In the present study, we investigated whether there is a relationship between the expression of TLR4 or TLR9 and the clinical or pathological changes in human lung cancer. Method Protein expression of TLR4 and TLR9 was assessed by using immunohistochemistry and western blotting. mRNA expressions of TLR4 and TLR9 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). Results High TLR4 and TLR9 mRNA signal intensity was found in the majority of lung cancer specimens. In contrast, tumor-free lung tissue showed lower signal intensity. Consistently, the low amount of TLR4 and TLR9 protein expression was found in tumor-free lung tissue, while they were strongly expressed in lung cancer tissue. In addition, we found for the first time that the differentiation degree of tumor cells was positively correlated with the expression level of TLR4. There was no relationship between the expressions of TLR4 or TLR9 and patients’ age, gender, smoking, the histological type of tumor, lymph node metastasis, and tumor node metastases (TNM) stage. Conclusions We found that both mRNA and protein levels of TLR4 and TLR9 were strongly expressed in lung cancer tissue. In addition, we reported for the first time a positive correlation between the expression level of TLR4 and malignancy of lung cancer. These results suggested that TLR4 and TLR9 may be involved in the development of lung cancer which may have the potentials for the treatment of this malignant tumor.

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Abbreviations

TLR:

Toll-like receptor

TNM:

Tumor node metastases

LRR:

Leucine-rich repeat

TIR:

Toll/IL-1 receptor

PAMP:

Pathogen associated molecular patterns

dsRNA:

Double-stranded RNA

AP-1:

Activator protein-1

NF-κB:

Nuclear factor-κB

LPS:

Lipopolysaccharide

CpG-ODN:

Cytidylyl phosphate guanosine oligodeoxynucleoside

CXCR:

CXC chemokine receptor

IL-8:

Interleukin-8

CTL:

Cytotoxicity lymphocyte

DC:

Dendritic cells

NSCLC:

Non-small cell lung carcinoma

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Acknowledgments

This work was supported by foundations. We would like to thank Mr. J Liu and D-B Wang for their excellent technical assistants. We would like to thank Dr. Jiang-Ning Zhou from University of Science and Technology of China for support. We also would like to thank Charlean Luellen from University of Tennessee Health Science Center, Memphis Department of Medicine.

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Correspondence to Rong-Yu Liu.

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Zhang, YB., He, FL., Fang, M. et al. Increased expression of Toll-like receptors 4 and 9 in human lung cancer. Mol Biol Rep 36, 1475–1481 (2009). https://doi.org/10.1007/s11033-008-9338-9

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  • DOI: https://doi.org/10.1007/s11033-008-9338-9

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