Cutting Edge: Toll-Like Receptor 4 (TLR4)-Deficient Mice Are Hyporesponsive to Lipopolysaccharide: Evidence for TLR4 as the Lps Gene Product
Abstract
The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-κB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.
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Ischemia/reperfusion induces interferon stimulated gene expression in microglia
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Understanding and Modulating Mammalian-Microbial Communication for Improved Human Health
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- Authors
- Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S.
- Affiliations
- Hyogo Medical University (JP)
- Asahi University (JP)
- Research Institute, International Medical Center of Japan , Tokyo ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-04-01
- Volume
- 162
- Issue
- 7
- Pages
- 3749-3752
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1978926805
- Cited by
- 3,374
- References
- 16
- Citations by year
- 2026: 33 · 2025: 38 · 2024: 56 · 2023: 67 · 2022: 57 · 2021: 74 · 2020: 90 · 2019: 86 · 2018: 94 · 2017: 113 · 2016: 114 · 2015: 107 · 2014: 128 · 2013: 129 · 2012: 147
- FWCI
- 53.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- TLR4, lipopolysaccharide, TLR4-deficient mice, C3H/HeJ mice, macrophage response, B cell response, NF-κB activation
- MeSH terms
- Amino Acid Sequence, Animals, B-Lymphocytes, Lipopolysaccharides, Membrane Glycoproteins, Mice, Inbred C3H, Molecular Sequence Data, Receptors, Cell Surface, Point Mutation, Macrophages, Peritoneal, Mice, Knockout, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice
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