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Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia

(2010) JOURNAL OF IMMUNOLOGY. 185(7). p.4385-4392
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Abstract
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-1 beta and IL-18. We show, however, that mice lacking both IL-1b 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-1 beta 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.
Keywords
APOPTOSIS, IN-VIVO, PROTEIN HMGB1, NALP3 INFLAMMASOME, PROINFLAMMATORY ACTIVITY, INTERLEUKIN-1-BETA CONVERTING-ENZYME, MOBILITY GROUP BOX-1, CASPASE-1 ACTIVATION, MICE DEFICIENT, RECOMBINANT HMGB1

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Citation

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MLA
Lamkanfi, Mohamed, et al. “Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia.” JOURNAL OF IMMUNOLOGY, vol. 185, no. 7, 2010, pp. 4385–92, doi:10.4049/jimmunol.1000803.
APA
Lamkanfi, M., Sarkar, A., Vande Walle, L., Vitari, A. C., Amer, mal A., Wewers, M. D., … Dixit, V. M. (2010). Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. JOURNAL OF IMMUNOLOGY, 185(7), 4385–4392. https://doi.org/10.4049/jimmunol.1000803
Chicago author-date
Lamkanfi, Mohamed, Anasuya Sarkar, Lieselotte Vande Walle, Alberto C Vitari, mal AO Amer, Mark D Wewers, Kevin J Tracey, Thirumala-Devi Kanneganti, and Vishva M Dixit. 2010. “Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia.” JOURNAL OF IMMUNOLOGY 185 (7): 4385–92. https://doi.org/10.4049/jimmunol.1000803.
Chicago author-date (all authors)
Lamkanfi, Mohamed, Anasuya Sarkar, Lieselotte Vande Walle, Alberto C Vitari, mal AO Amer, Mark D Wewers, Kevin J Tracey, Thirumala-Devi Kanneganti, and Vishva M Dixit. 2010. “Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia.” JOURNAL OF IMMUNOLOGY 185 (7): 4385–4392. doi:10.4049/jimmunol.1000803.
Vancouver
1.
Lamkanfi M, Sarkar A, Vande Walle L, Vitari AC, Amer mal A, Wewers MD, et al. Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. JOURNAL OF IMMUNOLOGY. 2010;185(7):4385–92.
IEEE
[1]
M. Lamkanfi et al., “Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia,” JOURNAL OF IMMUNOLOGY, vol. 185, no. 7, pp. 4385–4392, 2010.
@article{1055935,
  abstract     = {{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-1 beta and IL-18. We show, however, that mice lacking both IL-1b 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-1 beta 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.}},
  author       = {{Lamkanfi, Mohamed and Sarkar, Anasuya and Vande Walle, Lieselotte and Vitari, Alberto C and Amer, mal AO and Wewers, Mark D and Tracey, Kevin J and Kanneganti, Thirumala-Devi and Dixit, Vishva M}},
  issn         = {{0022-1767}},
  journal      = {{JOURNAL OF IMMUNOLOGY}},
  keywords     = {{APOPTOSIS,IN-VIVO,PROTEIN HMGB1,NALP3 INFLAMMASOME,PROINFLAMMATORY ACTIVITY,INTERLEUKIN-1-BETA CONVERTING-ENZYME,MOBILITY GROUP BOX-1,CASPASE-1 ACTIVATION,MICE DEFICIENT,RECOMBINANT HMGB1}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{4385--4392}},
  title        = {{Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia}},
  url          = {{http://doi.org/10.4049/jimmunol.1000803}},
  volume       = {{185}},
  year         = {{2010}},
}

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