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Synergistic effects of lipopolysaccharide and interferon- 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

Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai, Japan

Shunji Sugawara

Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai, Japan

Osamu Takeuchi

Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Shizuo Akira

Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Haruhiko Takada

Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai, Japan, dentht{at}mail.cc.tohoku.ac.jp

Lipopolysaccharide (LPS) and interferon (IFN)- synergistically induced interleukin-8 (IL-8) production in human monocytic THP-1 cells. IFN--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- . Unstimulated THP-1 cells were shown by flow cytometry to be practically devoid of membrane CD14 (mCD14). LPS and IFN- enhanced mCD14 and Toll-like receptor (TLR) 4 expression in THP-1 cells, respectively, and co-stimulation with LPS and IFN- induced higher levels of mCD14 and TLR4 expression than stimulation with either agent alone. LPS and IFN- alone each augmented MD-2 and MyD88 mRNA expression in THP-1 cells, and co-stimulation with LPS and IFN- markedly enhanced MD-2 and MyD88 mRNA expression in the cells compared to those with either LPS or IFN- alone. Anti-CD 14 and anti-TLR4 monoclonal antibodies almost completely inhibited IL-8 production induced by LPS plus IFN- in THP-1 cells. These findings suggest that combined stimulation of THP-1 cells with LPS and IFN- up-regulate mCD14, TLR4, MD-2 and MyD88 expression by these cells, which might be involved in synergistic IL-8 production by the cells.

Journal of Endotoxin Research, Vol. 9, No. 3, 145-153 (2003)
DOI: 10.1177/09680519030090030201


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