The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

Forouzandeh, Mahtab; Besen, Jaren; Keane, Robert W.; Vaccari, Juan Pablo de Rivero

doi:10.3389/fphar.2020.01238

Cited by 48 publications

(41 citation statements)

References 29 publications

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“…It is also critical to establish how these processes affect the inflammatory milieu in the thrombus microenvironment and in the systemic inflammatory response after cerebral ischemia. However, we have previously shown secreted inflammasome proteins caspase-1, ASC, IL-1β and IL-18 correlate with poorer outcomes in a variety of diseases or conditions of the nervous system and periphery, suggesting that these secreted inflammasome proteins are functional in inflammasome signaling ( Kerr et al, 2018a ; Kerr et al, 2018b ; Keane et al, 2018 ; Forouzandeh et al, 2020 ; Perez-Barcena et al, 2020 ; Scott et al, 2020 ), suggesting an important role in disease- or trauma-related inflammatory pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

et al. 2021

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The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1β through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinical and procedural outcomes of mechanical thrombectomy for AIS. Electron microscopy and immunofluorescence indicate the presence of NETs in thrombi of patients with AIS. Moreover, the inflammasome signaling proteins caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) were also present in clots associated with the marker of NETosis citrullinated histone 3H (CitH3). Analysis of protein levels by a simple plex assay show that caspase-1, ASC and interleukin (IL)-1β were significantly elevated in clots when compared to plasma of AIS patients and healthy controls, while IL-18 levels were lower. Moreover, multivariate analyses show that IL-1β levels in clots contribute to the number of passes to achieve complete recanalization, and that ASC, caspase-1 and IL-18 are significant contributors to time to recanalization. Thus, inflammasome proteins are elevated in NETs present in thrombi of patients with AIS that contribute to poor outcomes following stroke.

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Section: Discussionmentioning

confidence: 99%

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

et al. 2021

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“…We have recently shown that inflammasome proteins are good inflammatory biomarkers of traumatic brain injury, 16 , 36 stroke, 15 psoriasis, 37 and multiple sclerosis, 14 as well as mild cognitive impairment (MCI) and AD. 38 Interestingly, it has been suggested that AMD and AD share a common pathologic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

Weaver

Cyr

Vaccari³

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose Age-related macular degeneration (AMD) can result in severe vision loss and blurriness in the older population. The early and intermediate stages of AMD typically start without noticeable symptoms and can only be detected with a comprehensive eye exam. Because of the quiet onset of the disease, it is necessary to identify potential biomarkers to aid in the diagnosis, staging, and association with disease onset. Inflammasome signaling proteins are prominent biomarkers in the central nervous system, and the inflammasome has been shown to play a role in the innate inflammatory response in aging and AMD. Methods Serum from healthy controls and AMD patients were analyzed for the protein levels of Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18 and C-reactive protein (CRP) to determine cutoff points, positive and negative predictive values, and receiver operator characteristic curves, as well as univariate and multivariate linear and logistic regression models. Results ASC, IL-18, and CRP were elevated in the serum of AMD patients when compared to healthy controls. The area under the curve (AUC) for ASC was 0.98 with a cutoff point of 365.6 pg/mL, whereas IL-18 had an AUC of 0.73 and a cutoff point of 242.4 pg/mL, and the AUC for CRP was 0.67 with a cutoff point of 8,684,152 pg/mL. Levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R 2 of 0.1906, indicating that 19% of IL-18 could be explained by ASC protein levels in serum. Moreover, a logistic regression model for the diagnosis of AMD consists of ASC and having a diagnosis of hypertension, indicating that these two factors (elevated levels of ASC and a diagnosis of hypertension [HTN]) are associated with the diagnosis of AMD. Conclusions ASC, IL-18, and CRP are elevated in patients with AMD, and the protein levels of IL-18 are partially the result of ASC protein expression. Moreover, elevated protein levels of ASC in serum and a diagnosis of HTN increase the odds of patients having a diagnosis of AMD. Translational Relevance Biomarkers of AMD may be used to monitor disease risk, response to treatment and disease progression.

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“…Their findings indicate that inflammasome signaling pathway proteins, such as IL-18 and ASC, play a crucial role in inflammatory responses associated with psoriasis pathology. In the future, these proteins could be key biomarkers that help determine the diagnosis of psoriasis in this patient population [ 35 ].…”

Section: The Nlrp3 Inflammasome (In Psoriasis)mentioning

confidence: 99%

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

Ciążyńska

Olejniczak-Staruch

Sobolewska-Sztychny

et al. 2021

IJMS

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Inflammasomes are high-molecular-weight protein complexes that may cleave the two main proinflammatory cytokines, pro-interleukin-1β and pro-interleukin-18, into active forms, and contribute to psoriasis. Despite recent advances made in the pathogenesis of psoriasis, mainly studied as an autoimmune condition, activation of immune response triggers of psoriasis is still not completely understood. Recently, focus was placed on the role of inflammasomes in the pathogenesis of psoriasis. Multiple types of inhibitors and activators of various inflammasomes, inflammasome-related genes, and genetic susceptibility loci were recognized in psoriasis. In this systemic review, we collect recent and comprehensive evidence from the inflammasomes, NLRP1, NLRP3, and AIM2, in pathogenesis of psoriasis.

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The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

Cited by 48 publications

References 29 publications

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

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