Special Issue "Molecular Mechanism of Inflammasome Activation: Implications in Physiological and Pathological Conditions"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 September 2021).

Special Issue Editors

Dr. Concetta Saponaro
E-Mail Website
Guest Editor
IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
Interests: tumor biomarkers; tumor biology; tumor microenvironment; inflammasome
Dr. Raffaella Soleti
E-Mail Website
Guest Editor
SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, 49100 Angers, France
Interests: extracellular vesicles; metabolic diseases; cardiovascular diseases; oxidative stress; inflammation
Dr. Simona De Summa
E-Mail Website
Guest Editor
Molecular Diagnostics and Pharmacogenetics Unit-IRCCS-Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy
Interests: bioinformatics; genomics; transcriptomics; pathway
Dr. Antonia Cianciulli
E-Mail Website
Guest Editor
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy
Interests: microglia; neurons; neurodegeneration; neuroinflammation; signaling pathway; inflammation; cytokine

Special Issue Information

Dear Colleagues,

Research has overcome barriers and set new milestones in the life sciences by providing new tools for understanding many pathophysiological phenomena. In recent years, a topic of great interest has been the inflammasomes and their role in the cellular microenvironment.

Inflammasomes are oligomeric molecular platforms whose hyperactivation is due to genetic or environmental insult. To date, at least six different inflammasome signaling platforms have been reported, and they are involved in the signaling pathways of the innate immune system and in inflammatory reactions. Inflammasomes modulate the cytoskeleton, the production and maturation of cytokines, and cell death. Further, they play a key role in infections, autoimmune diseases, carcinogenesis and cancer progression, as well as cardiovascular and metabolic diseases. Inflammasome activity can also be influenced by variables such as the gastrointestinal microbiota, contributing to the progression of some diseases. The involvement of inflammasomes in numerous chronic-inflammation-related diseases increases interest in investigations regarding their place and use in clinical settings in the future, for the development of new prognostic/predictive biomarkers and therapeutic targets. This Special Issue focuses on the molecular mechanisms of inflammasomes activation and regulation, on the various pathway triggered, and on biological processes in physiological and pathological contexts. Contributions to this Issue can include original articles, reviews, short communications, and editorials.

Dr. Concetta Saponaro
Dr. Raffaella Soleti
Dr. Simona De Summa
Dr. Antonia Cianciulli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammasome
  • inflammation
  • cancer
  • neurobiology
  • cardiovascular biology
  • translational medicine
  • combined therapy

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Pharmacological and Epigenetic Regulators of NLRP3 Inflammasome Activation in Alzheimer’s Disease
Pharmaceuticals 2021, 14(11), 1187; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14111187 - 20 Nov 2021
Viewed by 361
Abstract
Activation of the NLRP3 inflammasome complex results in the production of IL-18, Caspase-1 and IL-1β. These cytokines have a beneficial role in promoting inflammation, but an excessive activation of the inflammasome and the consequent constitutive inflammatory status is a negative factor in human [...] Read more.
Activation of the NLRP3 inflammasome complex results in the production of IL-18, Caspase-1 and IL-1β. These cytokines have a beneficial role in promoting inflammation, but an excessive activation of the inflammasome and the consequent constitutive inflammatory status is a negative factor in human pathologies including Alzheimer’s Disease (AD). MicroRNAs (miR-NAs) target the 3′UTR region of NLRP3, preventing the activation of the inflammasome and inhibiting cytokine production. Because Stavudine (D4T), an antiretroviral drug, was recently shown to reduce inflammasome activation, we verified whether its effect is mediated by miR-7-5p, miR-22-3p, miR-30e-5p and miR-223-3p: miRNAs that bind the NLRP3-mRNA-UTR region and interfere with protein translation, reducing NLRP3 activation. Peripheral blood mononuclear cells (PBMCs) of twenty AD patients and ten sex-matched Healthy Controls (HC) were stimulated with Lipopolysaccharides (LPS)+Amyloid-beta (Aβ42) in the absence/presence of D4T. Expression of genes within the inflammasome complex and of miRNAs was evaluated by RT-PCR; cytokines and caspase-1 production was measured by ELISA. Results have shown that: NLRP3, ASC, IL-1β and IL-18 expression, as well as IL-18, IL-1β and caspase-1 production, were significantly augmented (p < 0.05) in LPS+Aβ42-stimulated PBMCs of AD patients compared to HC. D4T reduced the expression of inflammasome genes and cytokine production (p < 0.005). miR-7-5p and miR-223-3p expression was significantly increased in LPS+Aβ42-stimulated PBMCs of AD patients (p < 0.05), and it was reduced by D4T in AD alone. In conclusion: miR-223-3p and mir-7-5p expression is increased in AD, but this does not result in down-regulation of NLRP3 inflammasome expression and of IL-1β and IL-18 production. D4T increased miRNA expression in HC but had an opposite effect in AD, suggesting that miRNA regulatory mechanisms are altered in AD. Full article
Show Figures

Figure 1

Article
Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy
Pharmaceuticals 2021, 14(10), 983; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14100983 - 27 Sep 2021
Viewed by 496
Abstract
We hypothesize that endothelial-specific thioredoxin-interacting protein knock-out (EC-TXNIP KO) mice will be more resistant to the neurovascular damage (hemorrhagic-transformation-HT) associated with hyperglycemia (HG) in embolic stroke. Adult-male EC-TXNIP KO and wild-type (WT) littermate mice were injected with-streptozotocin (40 mg/kg, i.p.) for five consecutive [...] Read more.
We hypothesize that endothelial-specific thioredoxin-interacting protein knock-out (EC-TXNIP KO) mice will be more resistant to the neurovascular damage (hemorrhagic-transformation-HT) associated with hyperglycemia (HG) in embolic stroke. Adult-male EC-TXNIP KO and wild-type (WT) littermate mice were injected with-streptozotocin (40 mg/kg, i.p.) for five consecutive days to induce diabetes. Four-weeks after confirming HG, mice were subjected to embolic middle cerebral artery occlusion (eMCAO) followed by tissue plasminogen activator (tPA)-reperfusion (10 mg/kg at 3 h post-eMCAO). After the neurological assessment, animals were sacrificed at 24 h for neurovascular stroke outcomes. There were no differences in cerebrovascular anatomy between the strains. Infarct size, edema, and HT as indicated by hemoglobin (Hb)-the content was significantly higher in HG-WT mice, with or without tPA-reperfusion, compared to normoglycemic WT mice. Hyperglycemic EC-TXNIP KO mice treated with tPA tended to show lower Hb-content, edema, infarct area, and less hemorrhagic score compared to WT hyperglycemic mice. EC-TXNIP KO mice showed decreased expression of inflammatory mediators, apoptosis-associated proteins, and nitrotyrosine levels. Further, vascular endothelial growth factor-A and matrix-metalloproteinases (MMP-9/MMP-3), which degrade junction proteins and increase blood-brain-barrier permeability, were decreased in EC-TXNIP KO mice. Together, these findings suggest that vascular-TXNIP could be a novel therapeutic target for neurovascular damage after stroke. Full article
Show Figures

Figure 1

Article
Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation
Pharmaceuticals 2021, 14(9), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090852 - 26 Aug 2021
Viewed by 1091
Abstract
NLR family pyrin domain containing 3 (NLRP3) inflammasome formation is triggered by the damaged mitochondria releasing reactive oxygen species. Doxycycline was shown to regulate inflammation; however, its effect on NLRP3 in cancer remains largely unknown. Therefore, we sought to determine the effect of [...] Read more.
NLR family pyrin domain containing 3 (NLRP3) inflammasome formation is triggered by the damaged mitochondria releasing reactive oxygen species. Doxycycline was shown to regulate inflammation; however, its effect on NLRP3 in cancer remains largely unknown. Therefore, we sought to determine the effect of doxycycline on NLRP3 regulation in cancer using an in vitro model. NLRP3 was activated in a prostate cancer cell line (PC3) and a lung cancer cell line (A549) before treatment with doxycycline. Inflammasome activation was assessed by analyzing RNA expression of NLRP3, Pro-CASP-1, and Pro-IL1β using RT-qPCR. Additionally, NLPR3 protein expression and IL-1β secretion were analyzed using Western blot and ELISA, respectively. Tumor cell viability was determined using Annexin V staining and a cell proliferation assay. Cytokine secretion was analyzed using a 41Plex assay for human cytokines. Data were analyzed using one-way ANOVA model with Tukey’s post hoc tests. Doxycycline treatment decreased NLRP3 formation in PC3 and A549 cells compared to untreated and LPS only treated cells (p < 0.05). Doxycycline also decreased proliferation and caused cell death through apoptosis, a response that differed to the LPS-Nigericin mediated pyroptosis. Our findings suggest that doxycycline inhibits LPS priming of NLRP3 and reduces tumor progression through early apoptosis in cancer. Full article
Show Figures

Graphical abstract

Article
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation
Pharmaceuticals 2021, 14(6), 588; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060588 - 18 Jun 2021
Cited by 1 | Viewed by 1014
Abstract
Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the [...] Read more.
Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment. Full article
Show Figures

Figure 1

Review

Jump to: Research

Review
Contribution of Mitochondrial Dysfunction Combined with NLRP3 Inflammasome Activation in Selected Neurodegenerative Diseases
Pharmaceuticals 2021, 14(12), 1221; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14121221 - 25 Nov 2021
Viewed by 242
Abstract
Alzheimer’s disease and Parkinson’s disease are the most common forms of neurodegenerative illnesses. It has been widely accepted that neuroinflammation is the key pathogenic mechanism in neurodegeneration. Both mitochondrial dysfunction and enhanced NLRP3 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 3) inflammasome complex activity [...] Read more.
Alzheimer’s disease and Parkinson’s disease are the most common forms of neurodegenerative illnesses. It has been widely accepted that neuroinflammation is the key pathogenic mechanism in neurodegeneration. Both mitochondrial dysfunction and enhanced NLRP3 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 3) inflammasome complex activity have a crucial role in inducing and sustaining neuroinflammation. In addition, mitochondrial-related inflammatory factors could drive the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-18 (IL-18). The present review includes a broadened approach to the role of mitochondrial dysfunction resulting in abnormal NLRP3 activation in selected neurodegenerative diseases. Moreover, we also discuss the potential mitochondria-focused treatments that could influence the NLRP3 complex. Full article
Show Figures

Figure 1

Back to TopTop