Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation

Normand, Sylvain; Massonnet, Benoit; Delwail, Adriana; Favot, Laure; Cuisset, Laurence; Grateau, Gilles; Morel, Franck; Silvain, Christine; Lecron, Jean‐Claude

doi:10.1684/ecn.2009.0163

Cited by 41 publications

(17 citation statements)

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“…These findings are sustained by several studies in literature that report the involvement of IL-1α, IL-1β, IL-6 and IL-12 (p40) in the inflammatory processes of MKD [6,22,23]. Moreover, even if less marked, we also observed the involvement of IL-12 (p40) and GM-CSF, which also exert a pro-inflammatory activity and are able to coordinate the subsequent immune response [24,25].…”

Section: Resultssupporting

confidence: 61%

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Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Tricarico

Kleiner

Valencic

et al. 2014

IJMS

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Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD). One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

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Section: Resultssupporting

confidence: 61%

“…In particular, the IL-1 family is strongly believed to play a fundamental role in MKD inflammatory processes; indeed, it represents the major cytokine responsible for the systemic inflammatory effects observed in patients suffering from this disease [23]. …”

Section: Resultsmentioning

confidence: 99%

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Tricarico

Kleiner

Valencic

et al. 2014

IJMS

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“…76 Speculation about the pathogenetic role of inflammasomes has not been successful. 77,78 The characteristic feature of HIDS is elevation of serum IgD, 73,79 whereas IgA elevation is variable. 80 Ex vivo expression of TNF-alfa and IL-1ß is up-regulated during primary attacks.…”

Section: Hyper-igd Syndromementioning

confidence: 99%

Autoinflammation: From monogenic syndromes to common skin diseases

Nguyen

Cowen

Leslie

2013

Journal of the American Academy of Dermatology

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Autoinflammation is characterized by aberrant regulation of the innate immune system and often manifests as periodic fevers and systemic inflammation involving multiple organs, including the skin. Mutations leading to abnormal behavior or activity of the interleukin 1 beta (IL-1ß)-processing inflammasome complex have been found in several rare autoinflammatory syndromes, for which anticytokine therapy such as IL-1 or tumor necrosis factor-alfa inhibition may be effective. It is becoming clear that features of autoinflammation also affect common dermatoses, some of which were previously thought to be solely autoimmune in origin (eg, vitiligo, systemic lupus erythematosus). Recognizing the pathogenetic role of autoinflammation can open up new avenues for the targeted treatment of complex, inflammatory dermatoses.

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“…It is now thought that isoprenoid deficiency may affect signaling pathways involving enzymes such as Rac1, phosphatidylinositol 3-kinase, and PKB, which could activate caspase-1 and thus IL-1 and the inflammasome. Support for this has come from the finding that mononuclear cells from patients with MKD release elevated levels of IL-1β [54] and, importantly, from the fact that success has been reported with anakinra therapy [55,56]. There are no reports of the use of rilonacept or canakinumab in this disease.…”

Section: Mevalonate Kinase Deficiencymentioning

confidence: 99%

The Emerging Role of Interleukin-1β in Autoinflammatory Diseases

Lane

Lachmann

2011

Curr Allergy Asthma Rep

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The autoinflammatory syndromes are a group of multisystem disorders characterized by recurrent episodes of fever and systemic inflammation affecting the eyes, joints, skin, and serosal surfaces in the absence of an immune reaction. Recent advances have revealed the importance of interleukin-1β, not only in the pathogenesis of many of these rare inherited diseases, but also in acquired diseases. The development and availability of anti-interleukin-1β therapeutics have introduced the possibility of proof-of-concept studies, which are likely to further widen this field.

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Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation

Cited by 41 publications

References 0 publications

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Autoinflammation: From monogenic syndromes to common skin diseases

The Emerging Role of Interleukin-1β in Autoinflammatory Diseases

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