Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation

Prajwal Gurung; Mohamed Lamkanfi; Thirumala-Devi Kanneganti

doi:10.4049/jimmunol.1402951

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Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation

Journal article

Peer reviewed

Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation

Prajwal Gurung, Mohamed Lamkanfi and Thirumala-Devi Kanneganti

The Journal of immunology (1950), Vol.194(5), pp.2064-2067

03/01/2015

DOI: 10.4049/jimmunol.1402951

PMCID: PMC4340749

PMID: 25637014

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Abstract

The NLRP3 inflammasome is a multimeric protein complex that is assembled in response to a wide array of pathogens and danger-associated molecular patterns. Despite the ability of NLRP3 to respond to diverse cues, the mechanisms controlling the assembly of this complex are contested. Recently published studies showed that HOIL-1, a member of the linear ubiquitin chain assembly complex, contributes to activation of the NLRP3 inflammasome. SHARPIN, along with HOIP and HOIL-1, constitute the linear ubiquitin chain assembly complex. In this study, we examined whether SHARPIN is required for the activation of the NLRP3 inflammasome. Using Sharpin(cpdm) macrophages (deficient in SHARPIN expression), we demonstrate that SHARPIN is required for optimal activation of the NLRP3 inflammasome by both canonical and noncanonical stimuli. Furthermore, Sharpin(cpdm) macrophages had dramatic defects on both the NF-κB and MAPK pathways, suggesting a role in transcriptional priming of the NLRP3 inflammasome. In conclusion, our study identified SHARPIN as a novel regulator of the NLRP3 inflammasome.

Signal Transduction

NLR Family, Pyrin Domain-Containing 3 Protein

Mice, Inbred C57BL

Cells, Cultured

Gene Expression Regulation

NF-kappa B - immunology

Ubiquitin - genetics

Macrophages - cytology

Inflammasomes - genetics

Mice, Knockout

Carrier Proteins - genetics

Ubiquitin-Protein Ligases - immunology

Ubiquitination

Animals

NF-kappa B - genetics

Inflammasomes - immunology

Mitogen-Activated Protein Kinases - genetics

Transcription, Genetic

Mice

Mitogen-Activated Protein Kinases - immunology

Ubiquitin-Protein Ligases - genetics

Ubiquitin - immunology

Carrier Proteins - immunology

Macrophages - immunology

Details

Title: Subtitle: Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation
Creators: Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
Mohamed Lamkanfi - Department of Medical Protein Research, Flanders Institute of Biotechnology, Ghent B-9000, Belgium; and Department of Biochemistry, Ghent University, Ghent B-9000, Belgium
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; Thirumala-Devi.Kanneganti@StJude.org
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.194(5), pp.2064-2067
DOI: 10.4049/jimmunol.1402951
PMID: 25637014
PMCID: PMC4340749
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI101935 / NIAID NIH HHS 281600 / European Research Council R01 CA163507 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS AI101935 / NIAID NIH HHS R37 AI101935 / NIAID NIH HHS CA163507 / NCI NIH HHS AR056296 / NIAMS NIH HHS
Language: English
Date published: 03/01/2015
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094506902771

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