Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation

Han, Jun-Hyuk; Park, Jooho; Kang, Tae-Bong; Lee, Kwang-Ho

doi:10.3390/ijms22073318

Cited by 37 publications

(17 citation statements)

References 138 publications

(243 reference statements)

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“…It not only includes molecules involved in canonical and non-canonical inflammasome-related mechanisms, but also inflammasome-independent mechanisms of sensory inflammasome components, as repeatedly shown for NLRP3 [ 10 , 11 ]. In addition, intensive molecular links exist for different forms of regulated cell death [ 8 , 129 ] and a close and bi-directional relation to caspase-8 has been reported [ 11 , 130 ]. Caspase-8 was therefore included in our search of clinical data in relation to inflammasome components.…”

Section: Inflammasome Components In Akimentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1β and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

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Section: Inflammasome Components In Akimentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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“…However, recent evidence indicates that, during COVID-19 infection, caspase-8 seems to favour the production of cytokines and the activation of pro-inflammatory intermediates causing inflammatory types of cell death [ 126 ]. Caspase-8, for instance, is able to directly cleave pro-IL-1β, thus activating (and not inhibiting), through signal transduction, the necroptotic pathway, which is known to culminate in cell lysis accompanied with inflammation [ 128 ]. Moreover, caspase-8 has been shown to activate pyroptosis, another type of inflammatory cell death, by processing gasdermin D, a protein able to create plasma membrane pores that induced osmotic cellular lysis and release of inflammatory molecules [ 129 ].…”

Section: Nrf2 Activation As a Strategy For Covid-19 Treatmentmentioning

confidence: 99%

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.

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“…Notably, the mRNA expression of IL6 was downregulated in KIRP. Caspase8, encoded by CASP8 , was proved to activate caspase-1 and GSDMD cleavage, thus resulting in pyroptosis ( Orning et al, 2018 ; Han et al, 2021 ). Additionally, IRF1 was considered a transcription factor regulating pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Pyroptosis-Related Gene Signature for Predicting Prognosis in Kidney Renal Papillary Cell Carcinoma

Chen

Gao

et al. 2022

Front. Genet.

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Pyroptosis is defined as an inflammatory form of programmed cell death. Increasing studies have demonstrated that pyroptosis is closely related to tumor development and antitumor process. However, the role of pyroptosis in kidney renal papillary cell carcinoma (KIRP) remains obscure. In this study, we analyzed the expression of 52 pyroptosis-related genes (PRGs) in KIRP, of which 20 differentially expressed PRGs were identified between tumor and normal tissues. Consensus clustering analysis based on these PRGs was used to divided patients into two clusters, from which a significant difference in survival was found (p = 0.0041). The prognostic risk model based on six PRGs (CASP8, CASP9, CHMP2A, GPX4, IL6, and IRF1) was built using univariate Cox regression and LASSO–Cox regression analysis, with good performance in predicting one-, three-, and five-year overall survival. Kaplan–Meier survival analysis showed that the high-risk group had a poor survival outcome (p < 0.001) and risk score was an independent prognostic factor (HR: 2.655, 95% CI 1.192–5.911, p = 0.016). Immune profiling revealed differences in immune cell infiltration between the two groups, and the infiltration of M2 macrophages was significantly upregulated in the tumor immune microenvironment, implying that tumor immunity participated in the KIRP progression. Finally, we identified two hub genes in tumor tissues (IL6 and CASP9), which were validated in vitro. In conclusion, we conducted a comprehensive analysis of PRGs in KIRP and tried to provide a pyroptosis-related signature for predicting the prognosis.

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Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation

Cited by 37 publications

References 138 publications

Involvement of Inflammasome Components in Kidney Disease

Involvement of Inflammasome Components in Kidney Disease

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

A Novel Pyroptosis-Related Gene Signature for Predicting Prognosis in Kidney Renal Papillary Cell Carcinoma

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