Publications associées à Human proteinase 3 resistance to inhibition extends to alpha-2 macroglobulin

Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme

Background Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, i ...

Frontiers Media Sa2024

Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth

Freddy Radtke, Nadine Fournier, Etienne Meylan, Justine Pascual, Anita Bodac, Amber Dawn Bowler, Vincent Roh

Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a genetica ...

Springernature2024

Development of cysteine cathepsin inhibitors combined with cell type-specific delivery for the treatment of B-cell lymphoma and solid tumors

Aaron Simone Petruzzella

Cysteine cathepsins proteases are enzymes that play essential physiological roles, but their activity is also associated to different aspects of cancer progression and to the development of other diseases. Therefore, cysteine cathepsins are relevant and pr ...

EPFL2024

A Cluster of Evolutionarily Recent KRAB Zinc Finger Proteins Protects Cancer Cells from Replicative Stress–Induced Inflammation

Didier Trono, Priscilla Turelli, Sandra Eloise Kjeldsen, Cyril David Son-Tuyên Pulver, Evaristo Jose Planet Letschert, Filipe Amândio Brandão Sanches Vong Martins, Olga Marie Louise Rosspopoff, Joana Carlevaro Fita, Romain Forey, Florian Huber

Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe and inflammatory responses that promote immune rejection. KRAB domain-containing zinc fin ...

2024

Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity

Simona Frateschi, Sévan Stroh

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating proteases in vitro, highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3/St14 is relevant for rena ...

MDPI2023

Tracking spatiotemporal localisation and interactions of the innate immune sensor STING

Sophie Marie Elisabeth Rivara

Innate immunity, the very first line of defence of our cells, relies on the detection of universal pathogen- or danger-associated signals to launch an inflammatory response. A crucial part of our innate immune system is based on the recognition of out-of-c ...

EPFL2023

Investigating the effect of inflammation on the progression of B-cell lymphoma dissemination in the sentinel lymph node

Daniel Molina Romero

Lymphomas are a group of heterogeneous blood cancers that arise from lymphocytes. The two primary clinical classifications of lymphomas are Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). In particular, B-cell lymphoma refers to the malignancies ...

EPFL2023

Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway

Simona Frateschi

The serine protease prostasin (CAP1/Prss8, channel-activating protease-1) is a confirmed in vitro and in vivo activator of the epithelial sodium channel ENaC. To test whether proteolytic activity or CAP1/Prss8 abundance itself are required for ENaC activat ...

MDPI2022

Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by alpha-1 Antitrypsin

Florian Maria Wurm, Divor Kiseljak

For the treatment of severe COVID-19, supplementation with human plasma-purified alpha-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulato ...

MDPI2021

Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965

Kei Sakamoto, Katyayanee Neopane

SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compou ...

2021

Neonatal-Onset Familial Mediterranean Fever in an Infant with Human Parainfluenza Virus-4 Infection

Alessandro Borghesi

Unusual, severe infections or inflammatory episodes in newborns and infants are largely unexplained and often attributed to immature immune responses. Inborn errors of immunity (IEI) are increasingly recognized as the etiology of life-threatening inflammat ...

KARGER2021

Emodin Inhibits Inflammation, Carcinogenesis, and Cancer Progression in the AOM/DSS Model of Colitis-Associated Intestinal Tumorigenesis

Jelena Zaric

Colorectal cancer (CRC) is one of the most common cancer worldwide. Chronic inflammation contributes to CRC development and progression. Emodin, is a natural anthraquinone derivative with anti-oxidant, anti-inflammatory, and anti-tumor activities. We used ...

FRONTIERS MEDIA SA2021

Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGF beta

Marc-Olivier Sauvain, Freddy Radtke, Mauro Delorenzi, Nadine Fournier, Markus Germann, George Coukos, Amber Dawn Bowler

High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell re ...

2020

Tumor-Promoting Ly-6G(+) SiglecF(high) Cells Are Mature and Long-Lived Neutrophils

Etienne Meylan

Myeloid cells co-expressing the markers CD11b, Ly-6G, and SiglecF can be found in large numbers in murine lung adenocarcinomas and accelerate cancer growth by fostering tumor cell invasion, angiogenesis, and immunosuppression; however, some of these cells' ...

2020

Transport and programmed release of nanoscale cargo from cells by using NETosis

Daniel Meyer, Ardemis Anoush Boghossian, Alessandra Antonucci, Alice Judith Gillen

Cells can take up nanoscale materials, which has important implications for understanding cellular functions, biocompatibility as well as biomedical applications. Controlled uptake, transport and triggered release of nanoscale cargo is one of the great cha ...

ROYAL SOC CHEMISTRY2020

Durable and controlled depletion of neutrophils in mice

Caroline Anne-Lyse Contat, Etienne Meylan, Jessica Christine Vazquez, Justine Pascual, Julien Robert Rémi Faget, Gael Luis Boivin, Pierre-Benoit Bernard Ancey, Aspasia Gkasti

Neutrophils are an essential part of the innate immune system. To study their importance, experimental studies often aim to deplete these cells, generally by injecting anti-Ly6G or anti-Gr1 antibodies. However, these approaches are only partially effective ...

Nature Research2020

Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice

Johan Auwerx, Dongryeol Ryu, Jun Yong Kim, Ludger Jan Elzuë Goeminne

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in r ...

2020

Multicomponent Alginate-Derived Hydrogel Microspheres Presenting Hybrid Ionic-Covalent Network and Drug Eluting Properties

Sandrine Gerber, François Rémi Pierre Noverraz, Luca Szabó

The development of multifunctional encapsulation biomaterials could help the translation of cell‐based therapies into standard medical care. One of the major hurdles in the field of encapsulated cell transplantation is the current lack of materials present ...

Wiley-VHCA AG2020

Identification and characterisation of small-molecule inhibitors targeting STING

Simone Margret Haag

The recognition of pathogen-derived nucleic acids is a critical mechanism by which the innate immune system detects viral infection. Upon activation, nucleic acid sensors initiate the expression of type I interferons and other inflammatory mediators, subse ...

EPFL2019

Lysozyme-Induced Transcriptional Regulation of TNF-alpha Pathway Genes in Cells of the Monocyte Lineage

Paul Joseph Dyson, Florence Armand, Romain Hamelin, Gianni Sava, Isabelle Mireille Claude Schepens

Lysozyme is one of the most important anti-bacterial effectors in the innate immune system of animals. Besides its direct antibacterial enzymatic activity, lysozyme displays other biological properties, pointing toward a significant anti-inflammatory effec ...

2019