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Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2002, Vol. 99, No. 9, pp. 3427-3431 PHAGOCYTES Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-: a molecular basis for priming and synergism with bacterial lipopolysaccharide Daniela Bosisio, Nadia Polentarutti, Marina Sironi, Sergio Bernasconi, Kensuke Miyake, Ginette R. Webb, Michael U. Martin, Alberto Mantovani, and Marta Muzio From the Department of Immunology and Cell Biology, Mario Negri Institute, Milano, Italy; Department of Immunology, Saga Medical School, Japan; Molecular Cell Biology Unit, GlaxoSmithKline, Stevenage, United Kingdom; Pharmakologie, Medizinische Hochschule Hannover, Germany; and the Istituto di Patologia Generale, Università di Milano, Italy. In human monocytes and macrophages, interferon- (IFN) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of the accessory component MD-2 and of the adapter protein MyD88 was also increased. LPS increased TLR4 mRNA levels, but concomitantly decreased its surface expression. IFN counteracted the LPS-induced downregulation of TLR4. IFN-primed monocytes showed increased responsiveness to LPS in terms of phosphorylation of the interleukin-1 receptor-associated kinase (IRAK; immediately downstream of the MyD88 adapter protein), NF-kB DNA binding activity, and, accordingly, of cytokine (tumor necrosis factor  [TNF] and interleukin-12 [IL-12]) production. 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