The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4
Open accessAbstract
In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI.
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Cites
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Renal tubule injury: a driving force toward chronic kidney disease
Liu, B.-C., Tang, T.-T., Lv, L.-L., & Lan, H.-Y. (2018) · Kidney International · doi:10.1016/j.kint.2017.09.033 · Cited by 913
The immune system and kidney disease: basic concepts and clinical implications
Kurts, C., Panzer, U., Anders, H.-J., & Rees, A. J. (2013) · Nature Reviews Immunology · doi:10.1038/nri3523 · Cited by 696
Self-citationComplexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns
Schaefer, L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.619304 · Cited by 622
Self-citationDisseminated intravascular coagulation
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Metadata
- Authors
- Allam, R., Scherbaum, C. R., Darisipudi, M. N., Mulay, S. R., Hägele, H., Lichtnekert, J., Hagemann, J. H., Rupanagudi, K. V., Ryu, M., Schwarzenberger, C., Hohenstein, B., Hugo, C., Uhl, B., Reichel, C. A., Krombach, F., Monestier, M., Liapis, H., Moreth, K., Schaefer, L., & Anders, H.-J.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2012-08
- Volume
- 23
- Issue
- 8
- Pages
- 1375-1388
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2171249563
- Cited by
- 428
- References
- 51
- FWCI
- 21.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Allam, R., Scherbaum, C. R., Darisipudi, M. N., Mulay, S. R., Hägele, H., Lichtnekert, J., Hagemann, J. H., Rupanagudi, K. V., Ryu, M., Schwarzenberger, C., Hohenstein, B., Hugo, C., Uhl, B., Reichel, C. A., Krombach, F., Monestier, M., Liapis, H., Moreth, K., Schaefer, L., & Anders, H.-J. (2012). Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2011111077
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
