The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury
Open accessAbstract
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Macrophage activation via TLR4, a type of PRR, is also involved in gastric acid-induced ARDS and mouse ARDS models induced by SARS-CoV-1 or influenza virus H5N1 (355).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [355]
Experimental — accuracy not yet measuredIn the citing paper
“endogenous products such as oxidized phospholipids and matrix breakdown products also drive inflammation through TLR4 and probably other TLRs, providing a mechanism for perpetuating inflammation when microbial products are being cleared from the lungs (68,72).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,976
Self-citationDefective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · cited 2×
“Lung pathology were not affected in tlr3 (Yamamoto et al., 2003) or tlr9 (Hemmi et al., 2000) mutant mice (Figures S2A and S2B).”
BackgroundSelf-citationThe Acute Respiratory Distress Syndrome
Matthay, M. A. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605303342209 · Cited by 4,924
The Acute Respiratory Distress Syndrome
Ware, L. B., & Matthay, M. A. (2000) · New England Journal of Medicine · doi:10.1056/nejm200005043421806 · Cited by 4,666
Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3749 · Cited by 3,374
Self-citationRole of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., et al. (2003) · Science · doi:10.1126/science.1087262 · Cited by 3,286
Self-citationAngiotensin-converting enzyme 2 protects from severe acute lung failure
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., et al. (2005) · Nature · doi:10.1038/nature03712 · Cited by 2,453
Self-citationTargeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., & Akira, S. (1998) · Immunity · doi:10.1016/s1074-7613(00)80596-8 · Cited by 2,358
Self-citationConditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,098
Flagged first, then by citations
Cited by
Sorted by citations
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304
Self-citationPattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895
Self-citationIL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658
Self-citationPathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
Mogensen, T. H. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00046-08 · Cited by 3,296
Metadata
- Authors
- Imai, Y., Kuba, K., Neely, G. G., Yaghubian-Malhami, R., Perkmann, T., van Loo, G., Ermolaeva, M., Veldhuizen, R., Leung, Y. H. C., Wang, H., Liu, H., Sun, Y., Pasparakis, M., Kopf, M., Mech, C., Bavari, S., Peiris, J. S. M., Slutsky, A. S., Akira, S., Hultqvist, M., Holmdahl, R., Nicholls, J., Jiang, C., Binder, C. J., & Penninger, J. M.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Austrian Academy of Sciences (AT)
- University of Cologne (DE)
- Western University (CA)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- United States Army Medical Research Institute of Infectious Diseases (US)
- St. Michael's Hospital (CA)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Karolinska Institutet (SE)
- University of Hong Kong (HK)
- Corresponding author
- Imai, Yumiko
- Penninger, Josef M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 133
- Issue
- 2
- Pages
- 235-249
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7112336
- OpenAlex
- W2156613610
- Cited by
- 1,356
- References
- 60
- Citations by year
- 2026: 34 · 2025: 53 · 2024: 56 · 2023: 76 · 2022: 105 · 2021: 143 · 2020: 152 · 2019: 47 · 2018: 69 · 2017: 64 · 2016: 80 · 2015: 65 · 2014: 82 · 2013: 68 · 2012: 53
- FWCI
- 29.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1933 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- University of Pittsburgh
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (100233)
- Defense Threat Reduction Agency
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- acute lung injury, TLR4, TRIF, TRAF6, oxidized phospholipids, OxPAPC, oxidative stress, reactive oxygen species, NCF1, lung macrophages, H5N1 avian influenza, SARS, anthrax, innate immunity, respiratory distress syndrome
- MeSH terms
- Animals, Humans, Influenza, Human, Lung, Mice, Inbred C57BL, Orthomyxoviridae Infections, Phospholipids, Respiratory Distress Syndrome, Signal Transduction, Interleukin-6, NF-kappa B, Oxidative Stress, NADPH Oxidases, Adaptor Proteins, Vesicular Transport, Severe Acute Respiratory Syndrome, 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
