Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis

Italiani, Paola; Carlesi, Cecilia; Grazioli, Paola; Puxeddu, Ilaria; Borroni, Barbara; Bossù, Paola; Migliorini, Paola; Siciliano, Gabriele; Boraschi, Diana

doi:10.1186/1742-2094-11-94

Cited by 75 publications

(69 citation statements)

References 48 publications

(59 reference statements)

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“…On the other hand, mature IL1b which is released upon processing into the parenchyma could be degraded in the extracellular space in post-mortem tissue. However, our findings are in line with a previous study of Italiani and coworkers showing increased level of IL18 but not IL1b in serum of sALS patients (Italiani et al, 2014). In addition, we found that human astrocytes are the major cell type expressing NLRP3 and ASC.…”

Section: Discussionsupporting

confidence: 94%

“…Regarding human ALS, elevated levels of caspase 1 and IL18 have been reported in the plasma and in spinal cord tissue of sALS patients (Ilzecka et al, 2001;Italiani et al, 2014;Li et al, 2000). Although caspase 1activation and IL1b/IL18 release play a major role in ALS pathology, information about the responsible NOD-like receptors and neuronal cell types mediating inflammasome-dependent neuroinflammation is scarce.…”

Section: Discussionmentioning

confidence: 99%

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NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

Johann

Heitzer

Kanagaratnam

et al. 2015

Glia

206

167

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Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role in the pathogenesis of ALS and involves the activation of microglia and astrocytes. Intracellular inflammasome complexes are part of the innate immunity as they sense and execute host inflammatory responses. The best characterized component is the NLRP3 inflammasome comprised of the NLR protein NLRP3, the adaptor ASC and pro-caspase 1. The NLRP3 inflammasome is critical for the activation of caspase 1 and the processing and release of IL1β and IL18. In this study, we investigated the expression, activation and co-localization of the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal model for ALS as well as in post-mortem tissue of ALS patients. NLRP3 and its molecular components as well as IL1β were already detectable in SOD1 mice at a pre-symptomatic stage after 9 weeks and further increased in 14 week old animals. Spinal cord astrocytes were identified as the major cell type expressing NLRP3 components. In human ALS tissue, we also found increased NLRP3, ASC, IL18 and active caspase 1 levels compared to control patients. Our findings suggest that astroglial NLRP3 inflammasome complexes are critically involved in neuroinflammation in ALS.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

Johann

Heitzer

Kanagaratnam

et al. 2015

Glia

206

167

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“…Thus, negative regulation by IL-18BP may not be able to fully eliminate IL-18-induced inflammation. Notably, increased free IL-18 in conjunction with elevated levels of IL-18BP was also observed in another autoimmune disorder, systemic lupus erythematosus [39, 43], as well as in patients with sepsis syndrome and with sporadic amyotrophic lateral sclerosis [40, 45]. …”

Section: Discussionmentioning

confidence: 99%

Increased expression of IL-18 in the serum and islets of type 1 diabetics

Harms

Yarde

Guinn

et al. 2015

Molecular Immunology

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Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune-mediated destruction of pancreatic insulin-producing beta cells. Interleukin (IL)-18 is a pro-inflammatory cytokine implicated in the pathogenesis of a number of inflammatory diseases. Here, we analyzed IL-18 levels in the plasma of juveniles with T1D. Compared to control subjects, IL-18 levels were significantly elevated in patients with T1D. On the other hand, levels of IL-18 binding protein (IL-18BP) and IL-37, two negative regulators of IL-18 function, remained unchanged when comparing T1D to control samples. Notably, however, although IL-18BP levels were not elevated, IL-18 and IL-18BP were found to be positively correlated in type 1 diabetics. Even so, free, unbound IL-18 remained significantly increased in diabetic patients. Additionally, correlation studies also revealed that IL-18 and IL-18BP are positively correlated with HbA1c levels in T1D patients, suggesting a potential link between IL-18 and metabolic control in these patients. Finally, we observed a significant increase in IL-18 protein expression within human pancreatic islet specimens collected from type 1 diabetics. These results further expand our knowledge of the role of IL-18 in T1D, may give insight into common pathogenic mechanisms associated with metabolic control in both T1D and T2D, and suggest that targeting this cytokine may improve therapeutic outcomes for T1D patients.

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“…The circulating levels of both IL‐18 and IL‐18BP are elevated in numerous disease conditions, most likely being a non‐specific consequence of the disease status, although in some instances they could be involved in pathogenesis (; reviewed in ).…”

Section: Focus On the Il‐1r Familymentioning

confidence: 99%

The family of the interleukin‐1 receptors

Boraschi

Italiani

Weil

et al. 2017

Immunological Reviews

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246

219

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The extracellular forms of the IL-1 cytokines are active through binding to specific receptors on the surface of target cells. IL-1 ligands bind to the extracellular portion of their ligand-binding receptor chain. For signaling to take place, a non-binding accessory chain is recruited into a heterotrimeric complex. The intracellular approximation of the Toll-IL-1-receptor (TIR) domains of the 2 receptor chains is the event that initiates signaling. The family of IL-1 receptors (IL-1R) includes 10 structurally related members, and the distantly related soluble protein IL-18BP that acts as inhibitor of the cytokine IL-18. Over the years the receptors of the IL-1 family have been known with many different names, with significant confusion. Thus, we will use here a recently proposed unifying nomenclature. The family includes several ligand-binding chains (IL-1R1, IL-1R2, IL-1R4, IL-1R5, and IL-1R6), 2 types of accessory chains (IL-1R3, IL-1R7), molecules that act as inhibitors of signaling (IL-1R2, IL-1R8, IL-18BP), and 2 orphan receptors (IL-1R9, IL-1R10). In this review, we will examine how the receptors of the IL-1 family regulate the inflammatory and anti-inflammatory functions of the IL-1 cytokines and are, more at large, involved in modulating defensive and pathological innate immunity and inflammation. Regulation of the IL-1/IL-1R system in the brain will be also described, as an example of the peculiarities of organ-specific modulation of inflammation.

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Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis

Cited by 75 publications

References 48 publications

NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

Increased expression of IL-18 in the serum and islets of type 1 diabetics

The family of the interleukin‐1 receptors

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