title: 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.
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.
authors.affiliation: Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Siedlar
authors.forename: Anna
authors.initials: A
authors.lastname: Szaflarska
authors.forename: Antoni
authors.initials: A
authors.lastname: Szczepanik
authors.forename: Irena
authors.initials: I
authors.lastname: Ruggiero
authors.forename: Marion
authors.initials: M
authors.lastname: Frankenberger
authors.forename: Rafał
authors.initials: R
authors.lastname: Szatanek
authors.forename: Antoni
authors.initials: A
authors.lastname: Czupryna
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Popiela
authors.forename: Marek
authors.initials: M
authors.lastname: Zembala
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D021122:Protein Subunits; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases