The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Cellular Events Mediated by Lipopolysaccharide-stimulated Toll-like Receptor 4
Open accessAbstract
Lipopolysaccharide (LPS) stimulates multiple signaling events, including nuclear factor-kappaB (NF-kappaB) activity and the mitogen-activated protein (MAP) kinases, ERK, JNK, and p38 in LPS-responsive cells, resulting in transcriptional activation and cytokine generation. LPS-induced signaling via toll-like receptor 4 (TLR4) results in the activation of the transcription factor NF-kappaB. Since LPS activates other signaling cascades in responsive cells, the objective of this study was to determine whether such events are mediated by TLR4 in response to LPS. We generated human embryonic kidney cells (HEK293) that stably express TLR4 (HEK-TLR4) and examined their responsiveness to LPS by measuring NF-kappaB activity and production of interleukin-8 (IL-8). A trans-reporting system was used to measure the activity of Elk-1, an ETS-domain transcription factor targeted by MAP kinase pathways. LPS stimulated NF-kappaB reporter activity and IL-8 production but not Elk-1 activity in HEK-TLR4 cells. When MD-2, a protein associated with the extracellular domain of TLR4, was expressed in these cells, there was a marked increase in Elk-1 activity as well as ERK, JNK, and p38 MAP kinase phosphorylation in response to LPS. TLR4-mediated NF-kappaB reporter activity and IL-8 production was enhanced by the expression of MD-2. This study demonstrates that expression of both TLR4 and MD-2 is required for LPS to activate or augment the MAP kinase pathways, Elk-1 stimulation, and IL-8 generation.
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Cites
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MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
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Self-citationMyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways
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Regulation of transcription by MAP kinase cascades
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Cited by
LPS induction of gene expression in human monocytes
Guha, M., & Mackman, N. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(00)00149-2 · Cited by 2,304
Zarember, K. A., & Godowski, P. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.2.554 · Cited by 1,250
mRNA is an endogenous ligand for toll-like receptor 3
Karikó, K., Ni, H., Capodici, J., Lamphier, M., & Weissman, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310175200 · Cited by 1,062
Essential role of MD-2 in LPS responsiveness and TLR4 distribution
Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M., & Miyake, K. (2002) · Nature Immunology · doi:10.1038/ni809 · Cited by 1,020
Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex
da Silva Correia, J., Soldau, K., Christen, U., Tobias, P. S., & Ulevitch, R. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009164200 · Cited by 649
Metadata
- Authors
- Yang, H., Young, D. W., Gusovsky, F., & Chow, J. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 275
- Issue
- 27
- Pages
- 20861-20866
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2060222319
- Cited by
- 269
- References
- 28
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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