title: Synergistic effects of lipopolysaccharide and interferon-gamma in inducing interleukin-8 production in human monocytic THP-1 cells is accompanied by up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression.
abstract: Lipopolysaccharide (LPS) and interferon (IFN)-gamma synergistically induced interleukin-8 (IL-8) production in human monocytic THP-1 cells. IFN-gamma-primed THP-1 cells produced higher levels of IL-8 on stimulation with LPS than non-primed cells and the level correlated with duration of priming up to 24 h, although the level of IL-8 induced was most comparable to that induced by co-stimulation with LPS and IFN-gamma. Unstimulated THP-1 cells were shown by flow cytometry to be practically devoid of membrane CD14 (mCD14). LPS and IFN-gamma enhanced mCD14 and Toll-like receptor (TLR) 4 expression in THP-1 cells, respectively, and co-stimulation with LPS and IFN-gamma induced higher levels of mCD14 and TLR4 expression than stimulation with either agent alone. LPS and IFN-gamma alone each augmented MD-2 and MyD88 mRNA expression in THP-1 cells, and co-stimulation with LPS and IFN-gamma markedly enhanced MD-2 and MyD88 mRNA expression in the cells compared to those with either LPS or IFN-gamma alone. Anti-CD14 and anti-TLR4 monoclonal antibodies almost completely inhibited IL-8 production induced by LPS plus IFN-gamma in THP-1 cells. These findings suggest that combined stimulation of THP-1 cells with LPS and IFN-gamma up-regulate mCD14, TLR4, MD-2 and MyD88 expression by these cells, which might be involved in synergistic IL-8 production by the cells.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Riyoko
authors.initials: R
authors.lastname: Tamai
authors.forename: Shunji
authors.initials: S
authors.lastname: Sugawara
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019779:Salmonella enterica / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D016209:Interleukin-8; C495377:LY96 protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007371:Interferon-gamma