The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Flagellin, a Novel Mediator of Salmonella -Induced Epithelial Activation and Systemic Inflammation: IκBα Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction
Abstract
Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 μg/ml) induces IκBα degradation, NF-κB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-κB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (∼10 μg/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (∼300 μg/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin’s actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-γ and TNF-α, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 μg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.
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Cites
Defective 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
Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
Xie, Q. W., Kashiwabara, Y., & Nathan, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37600-7 · Cited by 2,212
Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2
Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., & Kirschning, C. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17406 · Cited by 1,704
Cell Activation and Apoptosis by Bacterial Lipoproteins Through Toll-like Receptor-2
Aliprantis, A. O., Yang, R.-B., Mark, M. R., Suggett, S., Devaux, B., Radolf, J. D., Klimpel, G. R., Godowski, P., & Zychlinsky, A. (1999) · Science · doi:10.1126/science.285.5428.736 · Cited by 1,474
Yoshimura, A., Lien, E., Ingalls, R. R., Tuomanen, E., Dziarski, R., & Golenbock, D. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.1.1 · Cited by 1,234
Jung, H. C., Eckmann, L., Yang, S. K., Panja, A., Fierer, J., Morzycka-Wroblewska, E., & Kagnoff, M. F. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117676 · Cited by 1,197
Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products
Lien, E., Sellati, T. J., Yoshimura, A., Flo, T. H., Rawadi, G., Finberg, R. W., Carroll, J. D., Espevik, T., Ingalls, R. R., Radolf, J. D., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33419 · Cited by 918
Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages
Underhill, D. M., Ozinsky, A., Smith, K. D., & Aderem, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14459 · Cited by 827
Hirschfeld, M., Kirschning, C. J., Schwandner, R., Wesche, H., Weis, J. H., Wooten, R. M., & Weis, J. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.5.2382 · Cited by 657
Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry
Eckmann, L., Kagnoff, M. F., & Fierer, J. (1993) · Infection and Immunity · doi:10.1128/iai.61.11.4569-4574.1993 · Cited by 654
Cited by
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742
The role of motility as a virulence factor in bacteria
Josenhans, C., & Suerbaum, S. (2002) · International Journal of Medical Microbiology · doi:10.1078/1438-4221-00173 · Cited by 658
Berkes, J., Viswanathan, V. K., Savkovic, S. D., & Hecht, G. (2003) · Gut · doi:10.1136/gut.52.3.439 · Cited by 601
Metadata
- Authors
- Eaves-Pyles, T., Murthy, K., Liaudet, L., Virág, L., Ross, G., Soriano, F. G., Szabó, C., & Salzman, A. L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-01
- Volume
- 166
- Issue
- 2
- Pages
- 1248-1260
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1940453590
- Cited by
- 270
- References
- 38
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Flagellin, a Novel Mediator of Salmonella -Induced Epithelial Activation and Systemic Inflammation: IκBα Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction. https://app.cochat.ai/papers/10.4049/jimmunol.166.2.1248
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- Eaves-Pyles, T., Murthy, K., Liaudet, L., Virág, L., Ross, G., Soriano, F. G., Szabó, C., & Salzman, A. L. (2001). Flagellin, a Novel Mediator of Salmonella -Induced Epithelial Activation and Systemic Inflammation: IκBα Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction. The Journal of Immunology. https://doi.org/10.4049/jimmunol.166.2.1248
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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