Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes

Elena Viganò, Catherine Emma Diamond, Roberto Spreafico, Akhila Balachander, Radoslaw M. Sobota and Alessandra Mortellaro ()
Additional contact information
Elena Viganò: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Catherine Emma Diamond: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Roberto Spreafico: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Akhila Balachander: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Radoslaw M. Sobota: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)
Alessandra Mortellaro: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR)

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Monocytes promote the early host response to infection releasing key pro-inflammatory cytokines, such as IL-1β. The biologically inactive IL-1β precursor is processed to active form by inflammasomes, multi-protein complexes activating caspase-1. Human monocytes exhibit an unconventional one-step pathway of inflammasome activation in response to lipopolysaccharide (LPS) alone. Although this lineage-restricted mechanism is likely to contribute to the pathology of endotoxin shock, signalling pathways regulating this mechanism are currently unknown. Here we report that caspase-4 and caspase-5 mediate IL-1α and IL-1β release from human monocytes after LPS stimulation. Although caspase-4 remains uncleaved, caspase-5 undergoes rapid processing upon LPS treatment. We also identify an additional caspase-5 cleavage product in LPS-stimulated monocytes, which correlates with IL-1 secretion. This one-step pathway requires Syk activity and Ca2+ flux instigated by CD14/TLR4-mediated LPS internalization. Identification of caspase-4/5 as the key determinants of one-step inflammasome activation in human monocytes provides potential targets for therapeutic intervention in endotoxin shock.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9761 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9761

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9761

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().