International immunopharmacology
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Int. Immunopharmacol. · Apr 2011
Randomized Controlled TrialCord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies.
This study investigated the efficacy of cord blood-derived cytokine-induced killer (CB-CIK) biotherapy combined with second-line chemotherapy in treating advanced solid malignancies after first-line chemotherapy failure. Forty patients with advanced solid malignancies after first-line chemotherapy failure were divided into two groups: CB-CIK cells transfusion plus second-line chemotherapy (CB-CIK+Chemotherapy) group and second-line chemotherapy alone (Chemotherapy) group. The ORR and DCR were 30% and 80% in CB-CIK + Chemotherapy group compared with 15% and 70% in Chemotherapy group (P = 0.451 for ORR and P = 0.716 for DCR) respectively. ⋯ In vitro studies further revealed that CB-CIK cells could overcome drug resistance in cisplatin-resistant lung adenocarcinoma cell line A549/CDDP through downregulating ABCG-2 and P-gp and induce cytotoxicity through the high level expression of CD3, CD56, FasL, and CD69. This could explain why CB-CIK could have synergistic effects with second-line chemotherapy shown in this clinical study. We concluded CB-CIK cells combined with second-line chemotherapy can significantly improve PFS and median survival compared with second-line chemotherapy alone in patients with advanced solid malignancies after first-line chemotherapy failure.
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Int. Immunopharmacol. · Apr 2011
Sildenafil attenuates LPS-induced pro-inflammatory responses through down-regulation of intracellular ROS-related MAPK/NF-κB signaling pathways in N9 microglia.
Excessive activation of microglial cells has been implicated in various neuroinflammation. The present study showed that sildenafil, a PDE5 inhibitor, significantly suppressed NO, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) production induced by LPS in microglial cells through decreasing the protein and/or mRNA expressions of inducible NO synthase (iNOS), IL-1β and TNF-α in a concentration-dependent manner. ⋯ Moreover, the increase of the expression of gp91phox, a critical and catalytic subunit of NADPH oxidase, and the levels of intracellular reactive oxygen species (iROS) induced by LPS were markedly inhibited by sildenafil. In summary, these data suggest that sildenafil exerts its in vitro anti-inflammatory effect in LPS-activated N9 microglial cells by blocking nuclear factor-κB (NF-κB) and MAPKs activation, which may be partly due to its potent down-regulation of the NADPH-derived iROS production.
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Int. Immunopharmacol. · Dec 2010
Down-regulation of IL-6 production by astaxanthin via ERK-, MSK-, and NF-κB-mediated signals in activated microglia.
In this study, we investigated the effect of astaxanthin on IL-6 in activated microglial cells because excessive interleukin-6 (IL-6) production by activated brain microglia has been linked to many neurological disorders and proper regulation of IL-6 is critical for maintaining brain homeostasis. Astaxanthin inhibited lipopolysaccharide (LPS)-stimulated IL-6 mRNA and protein in BV-2 microglial cells. Moreover, LPS-induced p-IKKα, p-IκBα, and p-NF-κB p65 levels were all suppressed by astaxanthin. ⋯ Astaxathin also inhibited the secretion and mRNA expression of IL-6 in SDF-1α-stimulated microglial cells. SDF-1α-stimulated ERK1/2, MSK1, and NF-κB p65 phosphorylation were reduced by astaxanthin. Therefore, our results suggest that astaxanthin regulates IL-6 production through a p-ERK1/2-MSK-1- and p-NF-κB p65-dependent pathway in activated microglial cells.
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Int. Immunopharmacol. · Nov 2010
Loxoribine, a selective Toll-like receptor 7 agonist, induces maturation of human monocyte-derived dendritic cells and stimulates their Th-1- and Th-17-polarizing capability.
Recently, a guanosine analog, 7-allyl-7,8-dihydro-8-oxo-guanosine (loxoribine), has been identified as a selective Toll-like receptor (TLR)7 agonist. Bearing in mind the controversy regarding the expression of TLR7 by human myeloid dendritic cells (DCs) and its significance for functions of these cells, the goal of this study was to investigate the effect of loxoribine on differentiation, maturation and functions of human monocyte-derived (Mo)DCs. Immature MoDCs were obtained by cultivation of monocytes for 6 days with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. ⋯ Allogeneic CD4(+)T cells in co-culture with loxoribine-treated MoDCs proliferated more strongly, at lower DC/CD4(+)T-cell ratio (1:80), and secreted significantly higher levels of IL-17 and IFN-γ compared to the cultures with control MoDCs. The stimulatory effect of loxoribine on T helper (Th)1 polarization capability of MoDCs was further potentiated by ligation of CD40. In conclusion, our results show that loxoribine stimulated differentiation, maturation, allostimulatory as well as Th1 and Th17 polarization capability of human MoDCs and suggests that these effects might be associated with up-regulation of TLR7 expression, but not increased IFN-β production.
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Neutrophils are the first line of innate immune defense against infectious diseases. However, since their discovery by Elie Metchnikoff, they have always been considered tissue-destructive cells responsible for inflammatory tissue damage occurring during acute infections. Now, extensive research in the field of neutrophil cell biology and their role skewing the immune response in various infections or inflammatory disorders revealed their importance in the regulation of immune response. ⋯ Activated neutrophils provide signals for the activation and maturation of macrophages as well as dendritic cells. Neutrophils are also involved in the regulation of T-cell immune response against various pathogens and tumor antigens. Thus, the present review is intended to highlight the emerging role of neutrophils in the regulation of both innate and adaptive immunity during acute infectious or inflammatory conditions.