Expression and function of TLR1,TLR2 and TLR6 in PBMC from patients with ovarian cancer
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    Abstract:

    Objective:To explore the pathogenesis of ovarian cancer by investigating the expression of Toll-like receptor 1 (TLR1),TLR2 and TLR6 in patients with ovarian cancer. Methods:We collected peripheral blood mononuclear cells (PBMC) from 13 ovarian cancer patients,13 benign diseases controls,and 13 healthy normal controls. The expression levels of TLR1,TLR2 and TLR6 were measured by flow cytometry in monocytes,CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes. Quantitative real-time PCR was used to measure IL-1β,IL-6,IL-8,and TNF-α in the collected from cells treated with TLR1,TLR2 or TLR6 ligands. Results:TLR1,TLR2 and TLR6 were all expressed in PBMC and they were elevated in monocytes from all three groups. The expression of TLR1,TLR2 and TLR6 from monocytes were higher (P < 0.05) in ovarian cancer patients(69.13%,59.43%,52.99%,respectively) as compared with benign disease controls (34.34%,25.32%,15.21%,respectively) and healthy normal controls(36.31%,26.63%,16.43%,respectively),there was no difference between benign disease controls and the healthy normal controls. While between CD4+T cells,CD8+T cells,as well as among B cells,no significant difference was found. In concordance with the above results,there was an observable increased expression of inflammatory cytokine interleukin interleukin-1β (IL-1β) upon stimulated by HKLM (TLR2 ligand) in ovarian cancer patients compared to benign disease controls and healthy normal controls (F = 2.05,P < 0.05;F = 2.19,P < 0.05),while no significant difference was noticed between benign disease controls and healthy normal controls;IL-6 was also up-regulated in ovarian cancer patients(F = 1.40,P < 0.05;F = 1.99,P < 0.05) when compared with benign disease controls and healthy normal controls,while no significant difference was obvioused between benign disease controls and healthy normal controls;Furthermore,there were differences in IL-8,TNF-α among three groups. Conditioned medium with FSL-1 (TLR6 ligand) induced higher amounts of IL-6 expression in ovarian cancer patients than benign disease controls and healthy normal controls (F = 1.30,P < 0.05;F = 1.69,P < 0.05),while no difference was found between benign disease controls and healthy normal controls. In particular,all three groups did not show significant up-regulation of IL-1β,IL-8 or TNF-α production in response to FSL-1 stimulation. Moreover,stimulated with Pam3CSK4 (TLR1/2 ligand),IL-1β,IL-6,IL-8 or TNF-α didn’t show significant up-regulation among all three groups. Conclusion:TLR1,TLR2 and TLR6 were highly expressed in monocytes from ovarian cancer patients,and inflammatory reaction mediated by IL-1β,IL-6 may play an important role in driving ovarian tumor progression.

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徐 娟,王 芳,娄鉴芳,史新惠,黄 蕾,张淑平,柯 星,孙瑞红,彭启松. TLR1、TLR2和TLR6在卵巢癌患者PBMC细胞亚群中的表达和功能初探[J].南京医科大学学报(自然科学版英文版),2014,(12):1638-1643.

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  • Received:June 19,2014
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  • Online: December 26,2014
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