Cited by 3,374Immune Response and InflammationInflammasome and immune disordersNF-κB Signaling Pathways

Cutting Edge: Toll-Like Receptor 4 (TLR4)-Deficient Mice Are Hyporesponsive to Lipopolysaccharide: Evidence for TLR4 as the Lps Gene Product

Hoshino, Katsuaki, Takeuchi, Osamu, Kawai, Taro, Sanjo, Hideki, Ogawa, Tomohiko, Takeda, Yoshifumi, Takeda, Kiyoshi, Akira, Shizuo·1999·The Journal of Immunology

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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Crossref · 10.4049/jimmunol.162.7.3749

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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
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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