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The induction of cytokine synthesis by flagellin is mediated by a Toll-like receptor 5 (TLR5) signaling pathway. Although flagellin activation of the IL-1R-associated kinase and induction of TNF-alpha synthesis are dependent on TLR5 and not TLR4, we have found that flagellin stimulates NO in macrophages via a pathway that requires TLR5 and TLR4. Flagellin(More)
Flagellin is a potent activator of a broad range of cell types involved in innate and adaptive immunity. An increasing number of studies have demonstrated the effectiveness of flagellin as an adjuvant, as well as its ability to promote cytokine production by a range of innate cell types, trigger a generalized recruitment of T and B lymphocytes to secondary(More)
The murine macrophage cell line, P388D1, was transfected with expression plasmids containing a cDNA for the precursor or mature form of human interleukin (IL)-1 alpha or -1 beta, and the extent of IL-1 protein secretion was analyzed. The secretion of IL-1 beta from cells transfected with a cDNA encoding the mature IL-1 beta was approximately 15-fold greater(More)
Expression of IL-1 alpha and beta genes was studied in human blood PMN with close monitoring of the effects of contaminating mononuclear leukocytes (MNL). We provide evidence that PMN both transcribe and translate IL-1 alpha and beta genes after stimulation with LPS or IL-1 alpha. A combination of mouse thymocyte comitogen proliferation assay, ELISA, and(More)
Interleukin-1 (IL-1), a peptide hormone produced by activated macrophages, possesses the ability to modulate the proliferation, maturation and functional activation of a broad spectrum of cell types and may play a major role in the initiation and amplification of immune and inflammatory responses through its action on these diverse cell populations. IL-1(More)
Flagellin from a number of Gram-negative bacteria induces cytokine and nitric oxide production by inflammatory cell types. In view of the evidence that flagellin responsiveness is subject to modulation, we explored the possibilities that a prior exposure to flagellin might result in a state of reduced flagellin responsiveness or tolerance and that(More)
Cyclosporin A blocked production of the lymphokine interleukin 2 by activated T lymphocytes. In a human and a murine cell line this inhibition reflected an absence of interleukin 2 messenger RNA. Under conditions in which these cells are normally stimulated to secrete high levels of interleukin 2, they failed to do so in the presence of cyclosporin A. In(More)
Flagellins from Gram-negative bacteria activate inflammatory cells by a toll-like receptor 5 (TLR5)-dependent signaling pathway. We have examined the interaction between flagellin and TLR5 using an in vitro binding assay. Purified recombinant His-tagged flagellin from Salmonella enteritidis bound to TLR5 in detergent lysates from COS-1 cells transiently(More)
Flagella are locomotive organelles present on a wide range of bacteria and are important for the pathogenesis of many species. Cells of the innate immune system lack memory per se, but recognize conserved pathogen-associated molecular patterns (PAMPs) through a family of type I membrane receptors known as Toll-like receptors (TLRs). Flagellin, the major(More)
A recent study (Ogushi, K., Wada, A., Niidome, T., Okuda, T., Llanes, R., Nakayama, M., Nishi, Y., Kurazono, H., Smith, K. D., Aderem, A., Moss, J., and Hirayama, T. (2004) J. Biol. Chem. 279, 12213-12219) concluded that gangliosides serve as co-receptors for flagellin signaling via toll-like receptor 5 (TLR5). In view of several findings in this study that(More)