Abstract
Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a pivotal role in the detrimental inflammatory processes that participate to cerebral ischemic damage. After injury, it is produced by distinct cells of the neurovascular unit as an inactive precursor, pro-IL-1β. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1β into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1β levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9 prevents cytokine maturation. These findings further support the hypothesis that, under ischemia-reperfusion injury, cerebral elevation of IL-1β occurs via mechanisms other than caspase-1, likely involving gelatinases.
Keywords: Caspase-1, gelatinases, interleukin (IL)-1β, neuroinflammation, stroke.
Mini-Reviews in Medicinal Chemistry
Title:Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?
Volume: 16 Issue: 9
Author(s): Diana Amantea, Rossella Russo, Michelangelo Certo, Laura Rombolà, Annagrazia Adornetto, Luigi A. Morrone, Maria Tiziana Corasaniti and Giacinto Bagetta
Affiliation:
Keywords: Caspase-1, gelatinases, interleukin (IL)-1β, neuroinflammation, stroke.
Abstract: Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a pivotal role in the detrimental inflammatory processes that participate to cerebral ischemic damage. After injury, it is produced by distinct cells of the neurovascular unit as an inactive precursor, pro-IL-1β. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1β into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1β levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9 prevents cytokine maturation. These findings further support the hypothesis that, under ischemia-reperfusion injury, cerebral elevation of IL-1β occurs via mechanisms other than caspase-1, likely involving gelatinases.
Export Options
About this article
Cite this article as:
Amantea Diana, Russo Rossella, Certo Michelangelo, Rombolà Laura, Adornetto Annagrazia, Morrone A. Luigi, Corasaniti Tiziana Maria and Bagetta Giacinto, Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?, Mini-Reviews in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1389557516666160321112512
DOI https://dx.doi.org/10.2174/1389557516666160321112512 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs
Current Pharmaceutical Design Mechanisms of Neuronal Damage and Neuroprotection Underlying Ischemia/Reperfusion Injury after Physical Exercise
Current Drug Targets Coagulation Factor Xa Inhibition: Biological Background and Rationale
Current Topics in Medicinal Chemistry Immunotherapy in Invasive Fungal Infection - Focus on Invasive Aspergillosis
Current Pharmaceutical Design Artificial O2 Carriers: Status in 2005
Current Pharmaceutical Design Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Current Drug Targets Roles of SUMOylation in Heart Development and Cardiovascular Diseases
Current Molecular Medicine Patent on Biomarkers in Medical Research: A Focus on Neuropsychiatric Disorders
Recent Patents on Biomarkers Current and Future Therapeutic Strategies to Target Inflammation in Stroke
Current Drug Targets - Inflammation & Allergy Role of Free Radicals and Antioxidant Signaling in Skeletal Muscle Health and Pathology
Infectious Disorders - Drug Targets Peptides as Signaling Inhibitors for Mammalian MAP Kinase Cascades
Current Pharmaceutical Design Targeting Apoptotic Pathways in Myocardial Infarction: Attenuated by Phytochemicals
Cardiovascular & Hematological Agents in Medicinal Chemistry Necroptosis: Who Knew There were so Many Interesting Ways to Die?
CNS & Neurological Disorders - Drug Targets The Cancer Related Thrombotic Tendency in Sepsis
Current Drug Targets Regulation of Xanthine Oxidase Activity by Substrates at Active Sites via Cooperative Interactions between Catalytic Subunits: Implication to Drug Pharmacokinetics
Current Medicinal Chemistry Matrix Metalloproteinase Inhibition in Atherosclerosis and Stroke
Current Molecular Medicine Mechanisms of Endogenous Endothelial Repair in Stroke
Current Pharmaceutical Design Pharmacological Neuroprotection in Stroke: Rationale, State-of-the-art and Future Directions
Current Neuropharmacology Targeting the Toll-System in Cardiovascular Sciences
Recent Patents on Inflammation & Allergy Drug Discovery Type 2 Transglutaminase in Neurodegenerative Diseases: The Mitochondrial Connection
Current Pharmaceutical Design