Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death

England, Hazel; Summersgill, Holly; Edye, Michelle E.; Rothwell, Nancy J.; Brough, David

doi:10.1074/jbc.m114.557561

Cited by 139 publications

(124 citation statements)

References 39 publications

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“…141,[177][178][179] Moreover, extracellular ATP promotes the activation of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome in APCs, hence stimulating the processing and release of interleukin (IL)-1b and IL-18. 119,[180][181][182][183][184][185][186][187][188][189] In line with this notion, the immunogenic potential of cells succumbing to ICD can be significantly reduced by pharmacological or genetic interventions that limit the availability of ATP in the pericellular space, such as the administration of recombinant apyrase (an ATP-degrading enzyme) or the transfection-enforced overexpression of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1, best known as CD39), which converts ATP into ADP and AMP. 190 Intriguingly, CD39 and 5 0 -nucleotidase, ecto (NT5E, best known as CD73), which transforms AMP into adenosine, are often overexpressed by malignant tissues.…”

Section: Immunogenic Cell Death Signalingmentioning

confidence: 82%

Consensus guidelines for the detection of immunogenic cell death

et al. 2014

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Section: Immunogenic Cell Death Signalingmentioning

confidence: 82%

Consensus guidelines for the detection of immunogenic cell death

et al. 2014

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“…A common theme amongst IL-1a-eliciting stimuli is that they trigger lytic cell death (e.g. necrosis, pyroptosis, necroptosis), indicating that passive release during cell lysis is a major mechanism for IL-1a release [44]. Such a model explains the previously puzzling profile of IL-1a release by inflammasome agonists; Gross and co-workers showed that while IL-1b release by a range of NLRP3 agonists is fully NLRP3/ASC/caspase-1 dependent, IL-1a release is NLRP3/ASC/caspase-1-dependent upon cell stimulation with some NLRP3 agonists (nigericin, ATP, Candida) but partially or fully NLRP3/ASC/caspase-1-independent for others (the particulate or crystalline compounds, alum, TiO2, silica, monosodium urate crystals) [22].…”

Section: Passive Release Of Alarmins: Il-1a and Il-33mentioning

confidence: 99%

Mechanisms of unconventional secretion of IL-1 family cytokines

2015

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One of the most poorly understood processes in cell biology is the peculiar ability of specific leaderless proteins to be secreted via ER/Golgi-independent mechanisms ('unconventional protein secretion'). One such leaderless protein is the major immune-activating cytokine, interleukin-1β (IL-1β). Unusual amongst cytokines, IL-1β is expressed in the cytosol as an inactive precursor protein. It requires maturation by the caspase-1 protease, which itself requires activation upon immune cell sensing of infection or cell stress. Despite 25 years of intensive research into IL-1β secretory mechanisms, how it exits the cell is still not well understood. Here we will review the various mechanisms by which macrophages have been proposed to secrete IL-1 family cytokines, and the potential involvement of caspase-1 therein. Since aberrant IL-1β production drives inherited and acquired human diseases (e.g. autoinflammatory diseases, arthritic diseases, gout, Alzheimer's disease), elucidation of the IL-1β secretory pathway may offer new therapeutic opportunities for treatment across this wide range of human conditions.

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“…10,34 Although a reason for this specificity currently is unknown, a possible reason could be the nature of cell death perturbed in each autoinflammatory disorder. 9 Although necrotic cell death releases bioactive IL-1a, IL-1b requires caspase-1e and/or caspase-8emediated maturation and release. Thus, depending on the type of cell death that is instigated, either IL-1a or IL-1b could initiate and promote sterile inflammation, driving the disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

IL-1β and Caspase-1 Drive Autoinflammatory Disease Independently of IL-1α or Caspase-8 in a Mouse Model of Familial Mediterranean Fever

Sharma

Vogel

et al. 2017

The American Journal of Pathology

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Mutations in the gene encoding pyrin are associated with autoinflammatory disorder Familial Mediterranean Fever (FMF). A FMF-knock-in mouse strain that expresses chimeric pyrin protein with a V726A mutation (Mefv V726A/V726A ) was generated to model human FMF. This mouse strain shows an autoinflammatory disorder that is prevented by genetic deletion of IL-1 (IL-1) receptor or apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC). ASC-mediated cell death leads to the release of IL-1a and IL-1b, both of which signal through IL-1 receptor. Furthermore, caspase-1 and caspase-8 can interact with ASC to mediate secretion of IL-1 cytokines. The specific IL-1 cytokine instigating development of FMF and the enzymatic caspase involved in its secretion currently are unknown. In this study, we show that the autoinflammation observed in Mefv V726A/V726A mice is mediated specifically by IL-1b and not IL-1a. Furthermore, the disorder is dependent on the caspase-1eASC axis, whereas caspase-8 is dispensable. Concurrently, aberrant IL-1b release by Mefv V726A/V726A monocytes in response to stimulation with lipopolysaccharide also is dependent on the caspase-1eASC axis. In conclusion, our studies have uncovered a specific role for caspase-1emediated IL-1b release in the manifestation of FMF. (Am J Pathol 2017, 187: 236e244; http://dx

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Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death

Cited by 139 publications

References 39 publications

Consensus guidelines for the detection of immunogenic cell death

Consensus guidelines for the detection of immunogenic cell death

Mechanisms of unconventional secretion of IL-1 family cytokines

IL-1β and Caspase-1 Drive Autoinflammatory Disease Independently of IL-1α or Caspase-8 in a Mouse Model of Familial Mediterranean Fever

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