The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity
Open accessAbstract
The molecular mechanisms of acute kidney injury (AKI) remain unclear. Toll-like receptors (TLRs), widely expressed on leukocytes and kidney epithelial cells, regulate innate and adaptive immune responses. The present study examined the role of TLR signaling in cisplatin-induced AKI. Cisplatin-treated wild-type mice had significantly more renal dysfunction, histologic damage, and leukocytes infiltrating the kidney than similarly treated mice with a targeted deletion of TLR4 [Tlr4(-/-)]. Levels of cytokines in serum, kidney, and urine were increased significantly in cisplatin-treated wild-type mice compared with saline-treated wild-type mice and cisplatin-treated Tlr4(-/-) mice. Activation of JNK and p38, which was associated with cisplatin-induced renal injury in wild-type mice, was significantly blunted in Tlr4(-/-) mice. Using bone marrow chimeric mice, it was determined that renal parenchymal TLR4, rather than myeloid TLR4, mediated the nephrotoxic effects of cisplatin. Therefore, activation of TLR4 on renal parenchymal cells may activate p38 MAPK pathways, leading to increased production of inflammatory cytokines, such as TNF-alpha and subsequent kidney injury. Targeting the TLR4 signaling pathways may be a feasible therapeutic strategy to prevent cisplatin-induced AKI in humans.
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Cites
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Self-citationDAMPs, PAMPs and alarmins: all we need to know about danger
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TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity
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Self-citationTLR4 activation mediates kidney ischemia/reperfusion injury
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Cited by
Mechanisms of Cisplatin Nephrotoxicity
Miller, R. P., Tadagavadi, R. K., Ramesh, G., & Reeves, W. B. (2010) · Toxins · doi:10.3390/toxins2112490 · Cited by 1,622
Self-citationThe immune system and kidney disease: basic concepts and clinical implications
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Cisplatin nephrotoxicity: new insights and therapeutic implications
Tang, C., Livingston, M. J., Safirstein, R., & Dong, Z. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00631-7 · Cited by 548
Volarevic, V., Djokovic, B., Jankovic, M. G., Harrell, C. R., Fellabaum, C., Djonov, V., & Arsenijevic, N. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0518-9 · Cited by 438
McSweeney, K. R., Gadanec, L. K., Qaradakhi, T., Ali, B. A., Zulli, A., & Apostolopoulos, V. (2021) · Cancers · doi:10.3390/cancers13071572 · Cited by 363
Metadata
- Authors
- Zhang, B., Ramesh, G., Uematsu, S., Akira, S., & Reeves, W. B.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2008-05
- Volume
- 19
- Issue
- 5
- Pages
- 923-932
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2108352961
- Cited by
- 317
- References
- 56
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- green
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