Review
Immunology
Yang Li, Qianzhou Jiang
Summary: Inflammasomes are supramolecular platforms that respond to damage-associated and pathogen-associated patterns, activating caspases and leading to pyroptosis and cytokine secretion. The uncoupling preferences between pyroptosis and cytokine secretion have context-dependent effects and contribute to various pathological conditions. Precise coupling and uncoupling decisions are crucial for tissue repair and threat elimination.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Sohaib Nizami, Kanisa Arunasalam, Jack Green, James Cook, Catherine B. Lawrence, Tryfon Zarganes-Tzitzikas, John B. Davis, Elena Di Daniel, David Brough
Summary: Research findings indicate that HSP90 inhibitor EC144 effectively suppresses inflammatory processes, including the activation of NLRP3, secretion of IL-1β and IL-6. The alpha isoform of HSP90 plays a crucial role in inflammatory signaling.
Article
Immunology
Huijeong Ahn, Hansae Lee, Gilyoung Lee, Jeongho Park, Haan-Woo Sung, Eunsong Lee, Geun-Shik Lee
Summary: The study found that parabens could disrupt Gram-negative pathogen infection through the inhibition of non-canonical inflammasome activation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Nanoscience & Nanotechnology
Guofang Zhang, Wenhe Luo, Wenjie Yang, Su Li, Dongjie Li, Yanqiao Zeng, Yang Li
Summary: This review discusses the potential danger posed by ENM-induced immune response in the human body and the crucial roles played by IL-1 family cytokines in this process. The molecular mechanisms of IL-1 family cytokine activity triggered by ENMs are also reviewed.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2022)
Article
Immunology
Giacomo De Luca, Giulio Cavalli, Corrado Campochiaro, Cosimo Bruni, Alessandro Tomelleri, Lorenzo Dagna, Marco Matucci-Cerinic
Summary: Systemic sclerosis (SSc) is a rare and severe connective tissue disease characterized by endothelial and vascular damage, immune activation, leading to inflammation and fibrosis of skin and internal organs. Cardiac involvement is common in SSc, often asymptomatic initially, with myocardial fibrosis considered the immunopathologic hallmark. Interleukin (IL)-1 and inflammasome play key roles in SSc-heart inflammation, and targeted inhibition of IL-1 is proposed as a potential treatment strategy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Samuel Drinkall, Catherine B. Lawrence, Bernadino Ossola, Samuel Russell, Clare Bender, Nicola B. Brice, Lee A. Dawson, Michael Harte, David Brough
Summary: The NLRP3 inflammasome is a multi-protein complex responsible for inflammation and has been implicated in various diseases. The K+ channel THIK-1 is found to be involved in NLRP3 activation and may serve as a potential therapeutic target for inflammatory diseases.
Article
Biochemistry & Molecular Biology
Shi Yu, Jack Green, Rose Wellens, Gloria Lopez-Castejon, David Brough
Summary: The inhibition of V-ATPase has been shown to exacerbate LPS-induced NLRP3 inflammasome activation in primary human monocytes, leading to an alternative pathway characterized by NLRP3-dependent, K+ efflux-independent, ASC oligomerization and caspase-1 activation. This suggests that V-ATPases play additional roles during NLRP3 inflammasome activation in primary human monocytes.
Review
Biochemistry & Molecular Biology
Jun-Hyuk Han, Jooho Park, Tae-Bong Kang, Kwang-Ho Lee
Summary: Initially classified as an apoptotic caspase, caspase-8 has now been found to play significant roles in regulating inflammatory processes. Recent research has shown its involvement in modulating inflammatory responses, inflammasome activation, cell death, and cytokine induction. This review summarizes the latest advances in understanding how caspase-8 impacts inflammatory reactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Ruixiang Chen, Chengyu Yin, Jianqiao Fang, Boyi Liu
Summary: Chronic pain negatively affects patients' quality of life, and the dysregulation of NLRP3 inflammasome may contribute to the pathogenesis of chronic pain. Successful therapeutic approaches targeting NLRP3 inflammasome have been developed for chronic pain treatment.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Cardiac & Cardiovascular Systems
Luca Liberale, Fabrizio Montecucco, Lena Schwarz, Thomas F. Luscher, Giovanni G. Camici
Summary: Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) and Colchicine Cardiovascular Outcomes Trial (COLCOT) were the first two randomized clinical trials to demonstrate the effectiveness of specific anti-inflammatory treatments in cardiovascular prevention, confirming the involvement of specific inflammatory pathways in atherosclerotic cardiovascular disease. Other trials targeting multiple inflammasome-independent pathways failed to show benefit, highlighting the significance of balancing the risk of impaired host defense and infections with the prevention of major adverse cardiovascular events in patients with residual inflammatory risk.
CARDIOVASCULAR RESEARCH
(2021)
Article
Immunology
Lucia de Almeida, Savita Devi, Mohanalaxmi Indramohan, Qi-Quan Huang, Rojo A. Ratsimandresy, Richard M. Pope, Andrea Dorfleutner, Christian Stehlik
Summary: Canonical inflammasomes are innate immune protein scaffolds that activate inflammatory responses. Excessive activation of inflammasomes is associated with inflammatory diseases. This study found that the protein POP1 regulates the inflammatory response in gout and functions by interfering with crucial interactions within the inflammasome complex.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biophysics
Xingxing Ren, Menglin Tao, Xiaoming Liu, Lele Zhang, Mingsong Li, Zijuan Hai
Summary: In this study, we developed two activatable caspase-1-responsive fluorescence biosensors that can efficiently and rapidly monitor inflammasome activation, with the potential for clinical diagnosis of related inflammatory diseases.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Nanoscience & Nanotechnology
Dipika Nandi, James Forster III, Anujan Ramesh, Anh Nguyen, Hariharan Bharadwaj, Ashish Kulkarni
Summary: This study developed a liposomal nanoreporter platform for the spatiotemporal delivery of imaging probe and inhibitor, enabling the monitoring and regulation of inflammasome activation. It exhibited the ability to detect and reduce inflammasome activation in vitro and in vivo, and alleviated inflammation. This novel tool has high potential for the real-time monitoring and treatment of inflammasome-mediated diseases.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Editorial Material
Immunology
Cecilia Garlanda, Domenico Supino
Summary: The researchers in this study designed a new drug to selectively inhibit IL-1 by analyzing an IL-1 receptor missense mutation associated with un-leashed IL-1-mediated inflammation.
Article
Immunology
Debabrata Chowdhury, Jason C. Gardner, Abhijit Satpati, Suba Nookala, Santhosh Mukundan, Aleksey Porollo, Julio A. Landero Figueroa, Kavitha Subramanian Vignesh
Summary: This study reveals a negative regulation role of MT3 in controlling non-canonical inflammasome activation, by increasing intracellular zinc levels to inhibit caspase-11. MT3 suppresses activation of caspase-11 inflammasome and synergizes with caspase-11 in impairing antibacterial immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Clinical Neurology
Cathal J. Hannan, Daniel Lewis, Claire O'Leary, Carmine A. Donofrio, Dafydd G. Evans, Emma Stapleton, Simon R. Freeman, Simon K. Lloyd, Scott A. Rutherford, Charlotte Hammerbeck-Ward, David Brough, Stuart M. Allan, David Coope, Andrew T. King, Omar N. Pathmanaban
Summary: This review examines inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in vestibular schwannomas (VS). The study finds that VS microenvironment is characterized by an infiltrate of inflammatory cells, particularly macrophages. There is a relationship between inflammation and angiogenesis in growing VS. The review highlights the need for further mechanistic studies to understand the exact role of inflammation in VS.
JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE
(2022)
Article
Engineering, Biomedical
John P. Stone, Kavit R. Amin, Abbey Geraghty, Jak Kerr, Matthew Shaw, Dilan Dabare, Jason K. Wong, David Brough, Timothy R. Entwistle, Angeles Montero-Fernandez, James E. Fildes
Summary: Adding a kidney to limb perfusion circuit significantly improves perfusate biochemistry and reduces the risk of metabolic acidosis, while global perfusion is more homogeneous with combined limb-kidney perfusion.
Article
Neurosciences
James R. Cook, Anna L. Gray, Eloise Lemarchand, Ingo Schiessl, Jack P. Green, Mary C. Newland, Douglas P. Dyer, David Brough, Catherine B. Lawrence
Summary: Microglia function does not critically rely on VRAC, although VRAC plays an important role in cell volume regulation. It does not affect phagocytic activity, cell migration, or P2YR12-dependent chemotaxis. Loss of VRAC in microglia does not impact microglial morphology or the extent of ischemic damage. VRAC may be targetable in other CNS cell types.
Article
Immunology
Christopher Hoyle, Jack P. Green, Stuart M. Allan, David Brough, Eloise Lemarchand
Summary: This study found that metabolite derivatives of itaconate and fumarate can inhibit the activation of NLRP3 inflammasome and reduce the secretion of inflammatory cytokines, suggesting their potential therapeutic role in diseases such as multiple sclerosis.
Article
Health Care Sciences & Services
Sarah Fox, Laura J. E. Brown, Steven Antrobus, David Brough, Richard J. Drake, Francine Jury, Iracema Leroi, Adrian R. Parry-Jones, Matthew Machin
Summary: This study explores the benefits of co-design in the development of smartphone apps. Using Agile methodology and continuous user consultation, testing, and feedback, individuals living with dementia and their care partners were actively involved in co-designing an easy-to-use, accessible, and appealing mobile health app. Co-design resulted in multiple patient and care partner-led software alterations, improving the user-friendliness and acceptability of the product.
JMIR MHEALTH AND UHEALTH
(2022)
Article
Neurosciences
Samuel Drinkall, Catherine B. Lawrence, Bernadino Ossola, Samuel Russell, Clare Bender, Nicola B. Brice, Lee A. Dawson, Michael Harte, David Brough
Summary: The NLRP3 inflammasome is a multi-protein complex responsible for inflammation and has been implicated in various diseases. The K+ channel THIK-1 is found to be involved in NLRP3 activation and may serve as a potential therapeutic target for inflammatory diseases.
Article
Clinical Neurology
Cathal John Hannan, Daniel Lewis, Claire O'Leary, Mueez Waqar, David Brough, Kevin N. Couper, Douglas P. Dyer, Andy Vail, Calvin Heal, Joshua Macarthur, Christopher Cooper, Charlotte Hammerbeck-Ward, D. Gareth Evans, Scott A. Rutherford, Simon K. Lloyd, Simon Richard Mackenzie Freeman, David John Coope, Andrew T. King, Omar Nathan Pathmanaban
Summary: There is evidence that macrophage infiltration in the tumor microenvironment promotes the growth of vestibular schwannoma (VS). The efficacy of bevacizumab in NF2-associated VS demonstrates the value of targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.
Article
Multidisciplinary Sciences
Joseph Masison, Pedro Mendes
Summary: Computational models of cellular iron metabolism can be created more efficiently by using smaller sub-models that represent specific cellular structures. A model for ferritin iron sequestration kinetics was established and validated, and it was found that the concentration of FT has the greatest impact on overall sequestration dynamics. The model's flexibility makes it suitable for use in a variety of specific cell type models of iron metabolism.
Article
Biochemistry & Molecular Biology
Laura Gonzalez-Cofrade, Jack P. Green, Irene Cuadrado, Angel Amesty, Sandra Oramas-Royo, David Brough, Ana Estevez-Braun, Sonsoles Hortelano, Beatriz de las Heras
Summary: This study evaluated the potential anti-inflammatory activity of phenolic and quinonemethide nor-triterpenes isolated from Maytenus retusa and their derivatives through inhibition of the NLRP3 inflammasome. Triterpenes 6 and 14 showed the highest anti-inflammatory activity by significantly reducing caspase-1 activity, IL-1 beta secretion, and pyroptosis. Further characterization confirmed their selective inhibition of NLRP3 inflammasome without affecting AIM2 or NLRC4 inflammasome activation.
BIOORGANIC CHEMISTRY
(2023)
Review
Immunology
Grace E. Gregory, Kevin J. Munro, Kevin N. Couper, Omar N. Pathmanaban, David Brough
Summary: Sensorineural hearing loss is the most common type of hearing loss in adults, caused by various factors such as aging, noise exposure, toxins, and cancer. Inflammation, including auto-inflammatory diseases, has been found to contribute to hearing loss. The activation of resident macrophage cells in the inner ear and the NLRP3 inflammasome may play a role in hearing loss. This article discusses the potential of targeting the NLRP3 inflammasome and associated cytokines as therapeutic strategies for sensorineural hearing loss in different conditions.
CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Janet Storm, Grazia N. Camarda, Michael J. G. Haley, David Brough, Kevin N. Couper, Alister G. Craig
Summary: Monocytes are involved in the pro-inflammatory immune response during Plasmodium falciparum infection, but their role in malaria pathology is not clear. Activation of monocytes by infected erythrocytes (IE) potentially involves the NLRP3 inflammasome, leading to the production of IL-1 beta. In cerebral malaria, monocytes accumulate at IE sequestration sites in the brain microvascular and locally produced IL-1 beta may contribute to blood-brain barrier leakage. However, an in vitro model showed no significant effect on barrier function after co-culturing monocytes and IE.
Article
Biochemistry & Molecular Biology
Bali Lee, Christopher Hoyle, Rose Wellens, Jack P. Green, Fatima Martin-Sanchez, Daniel M. Williams, Billie J. Matchett, Paula I. Seoane, Hayley Bennett, Antony Adamson, Gloria Lopez-Castejon, Martin Lowe, David Brough
Summary: Inflammation driven by the NLRP3 inflammasome is triggered by disrupted endosome trafficking, leading to enhanced inflammasome activation and cytokine secretion. These findings provide insight into the spatial activation of the NLRP3 inflammasome and suggest potential therapeutic targets.
Article
Multidisciplinary Sciences
Jack P. Green, Lina Y. El-Sharkawy, Stefan Roth, Jie Zhu, Jiayu Cao, Andrew G. Leach, Arthur Liesz, Sally Freeman, David Brough
Summary: Inflammation driven by DNA sensors is important in disease pathogenesis. New inhibitors of DNA sensing, particularly AIM2, have been discovered. These inhibitors, namely 4-sulfonic calixarenes, bind competitively to the DNA-binding HIN domain, effectively inhibiting AIM2, cGAS, and TLR9, and showing potential against DNA-driven inflammatory responses. The drug suramin, due to its structural similarities, is also proposed as an inhibitor of DNA-dependent inflammation.
Article
Oncology
Grace E. Gregory, Abdurrahman I. Islim, Cathal John Hannan, Adam P. Jones, Charlotte Hammerbeck-Ward, Scott A. Rutherford, Simon R. Freeman, Simon Lloyd, Michel Kalamarides, Miriam J. Smith, Kevin Couper, Catherine A. McBain, Michael D. Jenkinson, David Brough, Andrew T. King, D. Gareth Evans, Omar N. Pathmanaban
Summary: NF2-schwannomatosis is a genetic syndrome associated with meningioma. Meningioma in NF2-schwannomatosis is a major cause of morbidity and mortality. The management of meningioma in NF2-schwannomatosis differs from sporadic tumors, with a focus on conservative management and surgical intervention if necessary.
NEURO-ONCOLOGY ADVANCES
(2023)
