Dataset Information

Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway.

ABSTRACT: Pleural tuberculosis (TB), together with lymphatic TB, constitutes more than half of all extrapulmonary cases. Pleural effusions (PEs) in TB are representative of lymphocytic PEs which are dominated by T cells. However, the mechanism underlying T lymphocytes homing and accumulation in PEs is still incompletely understood. Here we performed a comparative analysis of cytokine abundance in PEs from TB patients and non-TB patients by protein array analysis and observed that MCP-2/CCL8 is highly expressed in the TB-PEs as compared to peripheral blood. Meanwhile, we observed that CCR5, the primary receptor used by MCP-2/CCL8, is mostly expressed on pleural CD4(+) T lymphocytes. Furthermore, we found that infection with either Mycobacterium bovis Bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis H37Rv induced production of MCP-2/CCL8 at both transcriptional and protein level in Raw264.7 and THP-1 macrophage cells, mouse peritoneal macrophages as well as human PBMC monocyte-derived macrophages (MDMs). The induction of MCP-2/CCL8 by mycobacteria is dependent on the activation of TLR2/PI3K/Akt and p38 signaling pathway. We conclude that accumulation of MCP-2/CCL8 in TB-PEs may function as a biomarker for TB diagnosis.

SUBMITTER: Liu H

PROVIDER: S-EPMC3572057 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway.

Liu Haipeng H Liu Zhonghua Z Chen Jianxia J Chen Ling L He Xin X Zheng Ruijuan R Yang Hong H Song Peng P Weng Dong D Hu Haili H Fan Lin L Xiao Heping H Kaufmann Stefan H E SH Ernst Joel J Ge Baoxue B

PloS one 20130213 2

Pleural tuberculosis (TB), together with lymphatic TB, constitutes more than half of all extrapulmonary cases. Pleural effusions (PEs) in TB are representative of lymphocytic PEs which are dominated by T cells. However, the mechanism underlying T lymphocytes homing and accumulation in PEs is still incompletely understood. Here we performed a comparative analysis of cytokine abundance in PEs from TB patients and non-TB patients by protein array analysis and observed that MCP-2/CCL8 is highly expr ...[more]

PMID: 23418602

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Project description:Background and aimsRecent studies reveal the accumulation of myeloid derived suppressor cells (MDSCs) in human peripheral blood mononuclear cells (PBMCs) following HCV infection, which may facilitate and maintain HCV persistent infection. The mechanisms by which HCV induces MDSCs are poorly understood. In the present study, we investigated the mechanisms by which HCV induces MDSCs that lead to suppression of T cell proliferation and expansion of CD4+Foxp3+ regulatory T cells.MethodsPurified monocytes from healthy donors were cultured with HCV core protein (HCVc) or cell culture-derived HCV virions (HCVcc), and characterized the phenotype and function of these monocytes by flow cytometry, quantitative PCR, ELISA and western blot assays. In addition, peripheral blood from healthy donors and chronic HCV infected patients was collected, and MDSCs and CD4+CD25+CD127- regulatory T cells were analyzed by flow cytometry.ResultsBoth HCVc and HCVcc induced expression of IDO1, PD-L1 and IL-10, and significantly down-regulated HLA-DR expression in human monocytes. HCVc-treated monocytes triggered CD4+Foxp3+ Tregs expansion, and inhibited autologous CD4+ T cell activation in an IDO1-dependent fashion. Our results showed that HCV virions or HCV core proteins induced MDSC-like suppressive monocytes via the TLR2/PI3K/AKT/STAT3 signaling pathway. Monocytes derived from patients with chronic HCV infection displayed MDSCs characteristics. Moreover, the percentages of CD14+ MDSCs and CD4+CD25+CD127- Tregs in chronic HCV infected patients were significantly higher than healthy individuals, and the frequency of MDSCs correlated with CD4+CD25+CD127- Tregs.ConclusionsHCV induced MDSC-like suppressive monocytes through TLR2/PI3K/AKT/STAT3 signaling pathway to induce CD4+Foxp3+ regulatory T cells and inhibit autologous CD4+ T cell activation. It will be of interest to test whether antagonizing suppressive functions of MDSCs could enhance immune responses and virus control in chronic HCV infection.

Project description:BackgroundMandibular distraction osteogenesis (MDO) is a kind of endogenous tissue engineering technology that lengthens the jaw and opens airway so that a patient can breathe safely and comfortably on his or her own. Endothelial progenitor cells (EPCs) are crucial for MDO-related angiogenesis. Moreover, emerging evidence suggests that heat shock protein 20 (Hsp20) modulates angiogenesis under hypoxic conditions. However, the specific role of Hsp20 in EPCs, in the context of MDO, is not yet known. The aim of this study was to explore the expression of Hsp20 during MDO and the effects of Hsp20 on EPCs under hypoxia.MethodsMandibular distraction osteogenesis and mandibular bone defect (MBD) canine model were established. The expression of CD34, CD133, HIF-1α, and Hsp20 in callus was detected by immunofluorescence on day 14 after surgery. Canine bone marrow EPCs were cultured, with or without optimal cobalt chloride (CoCl2) concentration. Hypoxic effects, caused by CoCl2, were evaluated by means of the cell cycle, cell apoptosis, transwell cell migration, and tube formation assays. The Hsp20/KDR/PI3K/Akt expression levels were evaluated via immunofluorescence, RT-qPCR, and western blot. Next, EPCs were incorporated with either Hsp20-overexpression or Hsp20-siRNA lentivirus. The resulting effects were evaluated as described above.ResultsCD34, CD133, HIF-1α, and Hsp20 were displayed more positive in the callus of MDO compared with MBD. In addition, hypoxic conditions, generated by 0.1 mM CoCl2, in canine EPCs, accelerated cell proliferation, migration, tube formation, and Hsp20 expression. Hsp20 overexpression in EPCs significantly stimulated cell proliferation, migration, and tube formation, whereas Hsp20 inhibition produced the opposite effect. Additionally, the molecular mechanism was partly dependent on the KDR/PI3K/Akt pathway.ConclusionIn summary, herein, we present a novel mechanism of Hsp20-mediated regulation of canine EPCs via Akt activation in a hypoxic microenvironment.

Dataset Information

Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway.

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Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway.

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