Cutting Edge: Naturally Occurring Soluble Form of Mouse Toll-Like Receptor 4 Inhibits Lipopolysaccharide Signaling
Open accessAbstract
Toll-like receptors (TLRs) are a family of proteins playing important roles in host defense. Mice defective of functional TLR4 are hyporesponsive to LPS, suggesting that TLR4 is essential for LPS signaling. Here we report the cloning of an alternatively spliced mouse TLR4 (mTLR4) mRNA. The additional exon exists between the second and third exon of the reported mTLR4 gene and contains an in-frame stop codon. The alternatively spliced mRNA encodes 86 aa of the reported mTLR4 and an additional 36 aa. This alternatively spliced mTLR4 mRNA expressed a partially secretary 20-kDa protein, which we named soluble mTLR4 (smTLR4). In a mouse macrophage cell line, the exogenously expressed smTLR4 significantly inhibited LPS-mediated TNF-α production and NF-κB activation. Additionally, in mouse macrophages, LPS increased the mRNA for smTLR4. Taken together, our results indicate that smTLR4 may function as a feedback mechanism to inhibit the excessive LPS responses in mouse macrophages.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Soluble forms of TLR2 and TLR4 function as decoys competing with membrane-bound TLRs for ligand binding.
“soluble forms of TLR2 and TLR4 have been identified to function as decoy, competing with the membrane-bound forms of TLRs for ligands binding [123, 124]”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [123]
The citation lists haven’t been fetched yet
References 28 · Cited by 273
- Authors
- Iwami, K.-I., Matsuguchi, T., Masuda, A., Kikuchi, T., Musikacharoen, T., & Yoshikai, Y.
- Affiliations
- Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine , Nagoya ,
- Nagoya University (JP)
- Aichi Gakuin University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-12
- Volume
- 165
- Issue
- 12
- Pages
- 6682-6686
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1514955262
- Cited by
- 273
- References
- 28
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 14 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 18 · 2015: 14 · 2014: 14 · 2013: 9 · 2012: 6
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ono Pharmaceutical
- Japan Society for the Promotion of Science (JSPS-RFTF97L00703)
- 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 signaling, alternative splicing, feedback regulation, macrophages, TNF-alpha production, NF-κB activation, innate immunity, host defense
- MeSH terms
- Animals, Base Sequence, Cell Line, Cloning, Molecular, Cricetinae, Humans, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Molecular Sequence Data, Molecular Weight, Receptors, Cell Surface, RNA, Messenger, Solubility, T-Lymphocytes, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, CHO Cells, Alternative Splicing, DNA, Complementary, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
