Inflammasome biology, molecular pathology and therapeutic implications

Awad, Fawaz; Assrawi, Eman; Louvrier, Camille; Jumeau, Claire; Georgin‐Lavialle, Sophie; Grateau, Gilles; Amselem, Serge; Giurgea, Irina; Karabina, Sonia‐Athina

doi:10.1016/j.pharmthera.2018.02.011

Cited by 115 publications

(77 citation statements)

References 289 publications

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“…Cytoplasmic danger receptors that belong to the NLR protein family such as nucleotide-binding oligomerization domain-like receptor family leucine-rich repeat protein (NLRP) 1, NLRP3, and NLR family caspase recruitment domain containing 4 (NLRC4), or other types of danger receptors such as AIM2 (absent In melanoma 2), IFI-16 (interferon gamma inducible protein 16), RIG-1 (retinoic acid inducible gene-1), and MEFV (mediterranean fever) induce the formation of multi-protein inflammasomes in response to engagement by according ligands [3]. For this, binding of receptor-specific danger signals such as LPS, which specifically activates NLRP3, or flagellin, which is recognized by NLRC4, initiates inflammasome formation via inclusion of the adaptor protein ASC (activating signal cointegrator).…”

Section: Production Of Il-1β Requires Two Distinct Signalsmentioning

confidence: 99%

“…Of note, all IL-1 family members are expressed as zymogens and most require proteasomal cleavage to yield biologically active mature forms. Of these, pro-IL-1β and pro-IL-18 are unique as they are cleaved by activated inflammasomes [3]. These multi-protein complexes are assembled in response to exogenous and endogenous danger signals and induce activation of caspases that generate bioactive IL-1β and IL-18.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

319

221

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Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

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Section: Production Of Il-1β Requires Two Distinct Signalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

319

221

View full text Add to dashboard Cite

show abstract

“…Basal expression of NLRP3 is thought to be insufficient for NLRP3 activation in resting cells (Bauernfeind et al, 2009). Engagement of PAMPs or DAMPs with PRRs, such as TLRs or Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), leads to nuclear factor-κB (NF-κB) activation and NLRP3 gene transcription (He et al, 2016;Awad et al, 2018;Swanson et al, 2019). Also, interleukin-1 receptor-associated kinases 1 (IRAK1), as well as ubiquitin modifications, play an important role in post-transcriptional regulation in the priming step (Bauernfeind et al, 2009;Juliana et al, 2012).…”

Section: A Glimpse Inside Inflammasomesmentioning

confidence: 99%

Crosstalk Between Acid Sphingomyelinase and Inflammasome Signaling and Their Emerging Roles in Tissue Injury and Fibrosis

Guo

Pang

et al. 2020

Front. Cell Dev. Biol.

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“…Clarifying the dominant cytokine or pathway implicated in disease may lead to the development of targeted therapeutic strategies for autoinflammatory conditions, as reviewed in recent publications [60,61]. Recent work has looked at individuals with interferonopathies treated with JAK1/2 inhibitor baricitinib.…”

Section: Classificationmentioning

confidence: 99%

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

Moghaddas

Masters

2018

Clinical Science

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Monogenic autoinflammatory disorders are an increasingly heterogeneous group of conditions characterised by innate immune dysregulation. Improved genetic sequencing in recent years has led not only to the discovery of a plethora of conditions considered to be ‘autoinflammatory’, but also the broadening of the clinical and immunological phenotypic spectra seen in these disorders. This review outlines the classification strategies that have been employed for monogenic autoinflammatory disorders to date, including the primary innate immune pathway or the dominant cytokine implicated in disease pathogenesis, and highlights some of the advantages of these models. Furthermore, the use of the term ‘autoinflammatory’ is discussed in relation to disorders that cross the innate and adaptive immune divide. The utilisation of next-generation sequencing (NGS) in this population is examined, as are potential in vivo and in vitro methods of modelling to determine pathogenicity of novel genetic findings. Finally, areas where our understanding can be improved are highlighted, such as phenotypic variability and genotype–phenotype correlations, with the aim of identifying areas of future research.

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Inflammasome biology, molecular pathology and therapeutic implications

Cited by 115 publications

References 289 publications

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Crosstalk Between Acid Sphingomyelinase and Inflammasome Signaling and Their Emerging Roles in Tissue Injury and Fibrosis

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

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