Depressed tumor necrosis factor alpha and interleukin-12p40 production by peripheral blood mononuclear cells of gastric cancer patients: association with IL-1R-associated kinase-1 protein expression and disease stage |
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Authors: | Siedlar Maciej Szaflarska Anna Szczepanik Antoni Ruggiero Irena Frankenberger Marion Szatanek Rafał Czupryna Antoni Popiela Tadeusz Zembala Marek |
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Affiliation: | Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Krakow, Poland. |
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Abstract: | Our study investigated the ability of peripheral blood mononuclear cells (PBMCs) isolated from patients with different clinical stages of gastric cancer to produce proinflammatory (tumor necrosis factor alpha [TNFalpha], interleukin 12p40 [IL-12p40] and interleukin 6 [IL-6]) and antiinflammatory (interleukin-10 [IL-10]) cytokines after stimulation with lipopolysaccharide (LPS) or tumor cells, and its correlation with IL-1R-associated kinase-1 (IRAK-1) protein expression. The data showed that TNF production by tumor cell-stimulated PBMCs obtained from patients with advanced gastric cancer was significantly depressed in comparison to the control group. The response to LPS was less affected. IL-12p40 production was depressed in all stages of disease, while the release of IL-10 and IL-6 remained unchanged. Depressed tumor cell-induced TNF and IL-12p40 production was associated with diminished IRAK-1 protein expression in PBMC. These findings may suggest that in advanced gastric cancer (at least in some cancer patients) diminished IRAK-1 protein expression may be a novel mechanism responsible for or facilitating downregulation of innate immune response to tumor cells. |
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Keywords: | TNFα IL‐12p40 IL‐10 IL‐6 IRAK‐1 gastric cancer CD14+CD16+ monocytes |
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