Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines

Ibrahim, José-Noël; Jounblat, Rania; Delwail, Adriana; Abou-Ghoch, Joelle; Salem, Nabiha; Chouery, Éliane; Mégarbané, André; Medlej‐Hashim, Myrna; Lecron, Jean‐Claude

doi:10.1016/j.cyto.2014.06.012

Cited by 36 publications

(26 citation statements)

References 44 publications

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“…5,42 In line with these observations, we observed an increase in IL-1b release and caspase-1 cleavage in Mefv V726A/V726A monocytes after 48 hours of LPS stimulation ( Figure 4, A and B). Release of IL-1b from Mefv V726A/V726A monocytes was abolished in the absence of ASC or caspase-1 ( Figure 4C).…”

Section: Monocytessupporting

confidence: 75%

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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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Section: Monocytessupporting

confidence: 75%

“…FMF is an autoinflammatory disorder marked by increased production of inflammatory mediators and neutrophilia in both humans 42 and mice. 5 Both IL-1a and IL-1b are capable of instigating sterile inflammation and we previously have shown that these cytokines drive distinct neutrophilmediated autoinflammatory disorders.…”

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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“…Compared to controls, stimulated and non-stimulated PBMC from patients with familial Mediterranean fever showed increased secretion of IL-6 and TNFα during crisis, whereas that of IL-1β and IL-1α was increased only by LPS stimulated cells. Non-stimulated PBMC showed the lowest yield of IFN-γ and IL-4 [9]. During the febrile episodes of an autoinflammatory process characterized by periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy, the peripheral blood concentrations of IL-6, IL-8 and IL-1β were elevated, whereas those of IL-2, IL-4, IL-5 and IL-10 were insignificant [8].…”

Section: Discussionmentioning

confidence: 95%

High Temperature Affects Cytokine Release by Human Peripheral Blood Mononuclear Cells

Bessler

Djaldetti

2015

Int J Immunol Immunother

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Background: Fever is one of the leading signs of the inflammatory process and it is one of the mechanisms that activate the immune system to defend the organism from various pathogens. For this goal, the peripheral blood mononuclear cells (PBMC) are among the first to be mobilized by triggering their capacity for phagocytosis and inflammatory cytokine production. However, their activation in the living organism is the outcome of several factors, including fever. The aim of the present work was to examine the effect of elevated temperature only on the capacity of human PBMC to produce inflammatory cytokines Methods: Stimulated and non-stimulated PBMC from healthy donors were treated with 37°C and 40°C for 4 and 24 hours. At the end of the incubation period the level of TNFα, IL-1β, IL-6, IL-10, IL-1ra, IL-2 and IFNγ was detected using ELISA kits. Results: Non-stimulated PBMC incubated at 37°C produced similar amounts of TNFα and IL-1β at 4 and 24 hrs. The expression of IL-6, IL-10 and IL-1ra was higher after 24 hrs as compared with that produced after 4 hrs. As for LPS-stimulated cells the production of all cytokines tested was increased significantly during 24 hrs of incubation except for the level of TNFα that did not differ significantly between 4 and 24 hrs of stimulation. Non-stimulated PBMC did not secrete detectable amounts of IL-2 or IFNγ, and that produced by PMA/ionomycin stimulated cells was significantly higher after 24 hrs of incubation as compared to 4 hrs. Elevation of the incubation temperature from 37°C to 40°C caused various degrees of inhibition in the generation of both pro-and anti-inflammatory cytokines. Conclusions: Exposure of unstimulated and stimulated PBMC to 40°C induced various degrees of inhibition in the production of both pro-and anti-inflammatory cytokines compared to cells incubated at 37°C. This observation may clarify the way the immune cells react in cases with fever.

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“…These modifications include phosphorylation, ADPribosylation, and glycosylation and occur upon cell exposure to Clostridium toxins and in conditions of mevalonate kinase deficiency or proline-serine-threonine phosphataseinteracting protein 1 (PSTPIP1) gain-of-function [82,[108][109][110]. Hyper-activation of the pyrin inflammasome by MEFV-activating mutations causes Familial Mediterranean fever (FMF), a disease that is characterized by high levels of IL-1β, IL-6, IL-8, and IL-12, recurring fever episodes, arthritis, and low bone mass [83,111]. FMF is the most prevalent monogenic autoinflammatory disorder; it affects over 100,000 persons worldwide and causes sporadic and chronic symptoms [98].…”

Section: Nlrp3mentioning

confidence: 99%

Omnipresence of inflammasome activities in inflammatory bone diseases

Alippe

Mbalaviele

2019

Semin Immunopathol

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The inflammasomes are intracellular protein complexes that are assembled in response to a variety of perturbations including infections and injuries. Failure of the inflammasomes to rapidly clear the insults or restore tissue homeostasis can result in chronic inflammation. Recurring inflammation is also provoked by mutations that cause the constitutive assembly of the components of these protein platforms. Evidence suggests that chronic inflammation is a shared mechanism in bone loss associated with aging, dysregulated metabolism, autoinflammatory, and autoimmune diseases. Mechanistically, inflammatory mediators promote bone resorption while suppressing bone formation, an imbalance which over time leads to bone loss and increased fracture risk. Thus, while acute inflammation is important for the maintenance of bone integrity, its chronic state damages this tissue. In this review, we discuss the role of the inflammasomes in inflammation-induced osteolysis.

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Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines

Cited by 36 publications

References 44 publications

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

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

High Temperature Affects Cytokine Release by Human Peripheral Blood Mononuclear Cells

Omnipresence of inflammasome activities in inflammatory bone diseases

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