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Cited by 465

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia

Open access
Lamkanfi, Mohamed, Sarkar, Anasuya, Vande Walle, Lieselotte, Vitari, Alberto C, Amer, Amal O, Wewers, Mark D, Tracey, Kevin J, Kanneganti, Thirumala-Devi, Dixit, Vishva M·2010·The Journal of Immunology

Abstract

Endotoxin administration recapitulates many of the host responses to sepsis. Inhibitors of the cysteine protease caspase 1 have long been sought as a therapeutic because mice lacking caspase 1 are resistant to LPS-induced endotoxic shock. According to current thinking, caspase 1-mediated shock requires the proinflammatory caspase 1 substrates IL-1β and IL-18. We show, however, that mice lacking both IL-1β and IL-18 are normally susceptible to LPS-induced splenocyte apoptosis and endotoxic shock. This finding indicates the existence of another caspase 1-dependent mediator of endotoxemia. Reduced serum high mobility group box 1 (HMGB1) levels in caspase 1-deficient mice correlated with their resistance to LPS. A critical role for HMGB1 in endotoxemia was confirmed when mice deficient for IL-1β and IL-18 were protected from a lethal dose of LPS by pretreatment with HMGB1-neutralizing Abs. We found that HMGB1 secretion from LPS-primed macrophages required the inflammasome components apoptotic speck protein containing a caspase activation and recruitment domain (ASC), caspase 1 and Nalp3, whereas HMGB1 secretion from macrophages infected in vitro with Salmonella typhimurium was dependent on caspase 1 and Ipaf. Thus, HMGB1 secretion, which is critical for endotoxemia, occurs downstream of inflammasome assembly and caspase 1 activation.

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Crossref · 10.4049/jimmunol.1000803

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Metadata

Authors
Lamkanfi, M., Sarkar, A., Vande Walle, L., Vitari, A. C., Amer, A. O., Wewers, M. D., Tracey, K. J., Kanneganti, T.-D., & Dixit, V. M.
Venue
The Journal of Immunology
Published
2010-10-01
Volume
185
Issue
7
Pages
4385-4392
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2171487873
Cited by
465
References
12
FWCI
8.74
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia. https://app.cochat.ai/papers/10.4049/jimmunol.1000803
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Lamkanfi, M., Sarkar, A., Vande Walle, L., Vitari, A. C., Amer, A. O., Wewers, M. D., Tracey, K. J., Kanneganti, T.-D., & Dixit, V. M. (2010). Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1000803

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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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