Tags

Type your tag names separated by a space and hit enter

Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer.
Cancer Immunol Immunother 2015; 64(3):275-86CI

Abstract

Inflammation has been implicated in the initiation and progression of ovarian cancer (OC), the underlying mechanisms of which are still unclear. We hypothesized that the abnormal expression of Toll-like receptors (TLRs), which were potential activators of nuclear factor-kappa B p65 (NF-κB p65), could promote inflammation and tumorigenesis in OC. In this study, we characterized the expression of TLRs in peripheral blood mononuclear cells (PBMCs) and found TLR2 and TLR6 mRNAs levels to be higher in PBMCs from OC patients than in those from benign disease (BC) or healthy normal controls (NC). Flow cytometry analysis showed that TLR1, TLR2 and TLR6 were highly expressed in monocytes from OC patients, but not in those from control subjects. Consistently, inflammatory cytokines interleukin (IL)-1β and IL-6 were up-regulated in PBMCs from OC patients upon stimulation with Pam3CSK4 (TLR1 ligand) and HKLM (TLR2 ligand), compared with unstimulated PBMCs. Stimulation of PBMCs with TLR ligands led to activation of downstream signaling molecules in TLRs (MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65). We also discovered that SK-OV-3-secreted factors were potent PBMCs activators, leading to the production of IL-1β, IL-6 and IL-8 through activation of TLRs and downstream signaling molecules in PBMCs. Before coculturing with SK-OV-3, pretreatment of THP-1 cells or PBMCs with monoclonal antibodies against TLR1, TLR2 or TLR6 inhibited the production of IL-1β and IL-6 and activation of MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65. Our results provided new evidence that TLR1, TLR2 and TLR6 signaling was linked with inflammation in OC microenvironment.

Authors+Show Affiliations

Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25376541

Citation

Zhang, Xiaojie, et al. "Expression and Function of Toll-like Receptors in Peripheral Blood Mononuclear Cells From Patients With Ovarian Cancer." Cancer Immunology, Immunotherapy : CII, vol. 64, no. 3, 2015, pp. 275-86.
Zhang X, Xu J, Ke X, et al. Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer. Cancer Immunol Immunother. 2015;64(3):275-86.
Zhang, X., Xu, J., Ke, X., Zhang, S., Huang, P., Xu, T., ... Pan, S. (2015). Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer. Cancer Immunology, Immunotherapy : CII, 64(3), pp. 275-86. doi:10.1007/s00262-014-1632-x.
Zhang X, et al. Expression and Function of Toll-like Receptors in Peripheral Blood Mononuclear Cells From Patients With Ovarian Cancer. Cancer Immunol Immunother. 2015;64(3):275-86. PubMed PMID: 25376541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer. AU - Zhang,Xiaojie, AU - Xu,Juan, AU - Ke,Xing, AU - Zhang,Shuping, AU - Huang,Peijun, AU - Xu,Ting, AU - Huang,Lei, AU - Lou,Jianfang, AU - Shi,Xinhui, AU - Sun,Ruihong, AU - Wang,Fang, AU - Pan,Shiyang, Y1 - 2014/11/07/ PY - 2014/03/10/received PY - 2014/10/28/accepted PY - 2014/11/8/entrez PY - 2014/11/8/pubmed PY - 2015/4/29/medline SP - 275 EP - 86 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 64 IS - 3 N2 - Inflammation has been implicated in the initiation and progression of ovarian cancer (OC), the underlying mechanisms of which are still unclear. We hypothesized that the abnormal expression of Toll-like receptors (TLRs), which were potential activators of nuclear factor-kappa B p65 (NF-κB p65), could promote inflammation and tumorigenesis in OC. In this study, we characterized the expression of TLRs in peripheral blood mononuclear cells (PBMCs) and found TLR2 and TLR6 mRNAs levels to be higher in PBMCs from OC patients than in those from benign disease (BC) or healthy normal controls (NC). Flow cytometry analysis showed that TLR1, TLR2 and TLR6 were highly expressed in monocytes from OC patients, but not in those from control subjects. Consistently, inflammatory cytokines interleukin (IL)-1β and IL-6 were up-regulated in PBMCs from OC patients upon stimulation with Pam3CSK4 (TLR1 ligand) and HKLM (TLR2 ligand), compared with unstimulated PBMCs. Stimulation of PBMCs with TLR ligands led to activation of downstream signaling molecules in TLRs (MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65). We also discovered that SK-OV-3-secreted factors were potent PBMCs activators, leading to the production of IL-1β, IL-6 and IL-8 through activation of TLRs and downstream signaling molecules in PBMCs. Before coculturing with SK-OV-3, pretreatment of THP-1 cells or PBMCs with monoclonal antibodies against TLR1, TLR2 or TLR6 inhibited the production of IL-1β and IL-6 and activation of MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65. Our results provided new evidence that TLR1, TLR2 and TLR6 signaling was linked with inflammation in OC microenvironment. SN - 1432-0851 UR - https://www.unboundmedicine.com/medline/citation/25376541/Expression_and_function_of_Toll_like_receptors_in_peripheral_blood_mononuclear_cells_from_patients_with_ovarian_cancer_ L2 - https://dx.doi.org/10.1007/s00262-014-1632-x DB - PRIME DP - Unbound Medicine ER -