A5023620627- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- Advanced Glycation End Products research
- Tuberculosis Research and Epidemiology
- Infections and bacterial resistance
- Pharmacological Effects of Natural Compounds
- Polyamine Metabolism and Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fungal Infections and Studies
- Inflammasome and immune disorders
- Helicobacter pylori-related gastroenterology studies
- Barrier Structure and Function Studies
- Diagnosis and treatment of tuberculosis
- Fungal Biology and Applications
- Carbohydrate Chemistry and Synthesis
- Autophagy in Disease and Therapy
- Sphingolipid Metabolism and Signaling
- Ginseng Biological Effects and Applications
- Heme Oxygenase-1 and Carbon Monoxide
- Autoimmune and Inflammatory Disorders
- Erythrocyte Function and Pathophysiology
- Acute Kidney Injury Research
- Infectious Diseases and Mycology
- Hemoglobinopathies and Related Disorders
- Plant-based Medicinal Research
University of Surrey
2021-2025
Goethe University Frankfurt
2014-2019
RELX Group (United States)
2019
Exacerbated inflammation in renal ischemia–reperfusion injury, the major cause of intrinsic acute failure, is a key trigger kidney damage. During disease endogenous danger signals stimulate innate immune cells via Toll-like receptors (TLR)-2 and -4 accelerate inflammatory responses. Here we show that production soluble biglycan, small leucine-rich proteoglycan, induced during reperfusion it functions as agonist TLR-2/4. Biglycan-mediated activation TLR-2/4 initiates an response native...
Biglycan, a ubiquitous proteoglycan, acts as danger signal when released from the extracellular matrix. As such, biglycan triggers synthesis and maturation of interleukin-1β (IL-1β) in Toll-like receptor (TLR) 2-, TLR4-, reactive oxygen species (ROS)-dependent manner. Here, we discovered that autonomously regulates balance IL-1β production vitro vivo by modulating expression, activity stability NADPH oxidase (NOX) 1, 2 4 enzymes via different TLR pathways. In primary murine macrophages,...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on human primary endothelial cells vitro. show that mycolactone-induced changes morphology, adhesion, migration, and permeability are dependent at Sec61...
In its soluble form, the extracellular matrix proteoglycan biglycan triggers synthesis of macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization Toll-like receptors (TLRs) their adaptor molecules. However, respective downstream signaling events resulting in biglycan-induced production have not yet been defined. Here, we show that stimulates activation sphingosine kinase 1 (SphK1) a TLR4- Toll/interleukin (IL)-1R domain-containing inducing...
Buruli ulcer (BU) is a neglected tropical disease caused by subcutaneous infection with Mycobacterium ulcerans and its exotoxin mycolactone. BU displays coagulative necrosis widespread fibrin deposition in affected skin tissues. Despite this, the role of vasculature pathogenesis remains almost completely unexplored. We hypothesise that fibrin-driven ischemia can be an 'indirect' route to mycolactone-dependent tissue mechanism involving vascular dysfunction. Here, we tracked >900 vessels...
Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a devastating necrotizing skin disease. Key to its pathogenesis mycolactone, the exotoxin virulence factor that both immunosuppressive and cytotoxic. The discovery essential Sec61 translocon major cellular target of mycolactone explains much disease pathology, including immune blockade. inhibition leads loss in production nearly all cytokines from monocytes, macrophages, dendritic cells T cells, as well antigen presentation pathway...
The Mycobacterium ulcerans exotoxin, mycolactone, is responsible for the immunosuppression and tissue necrosis that characterizes Buruli ulcer. Mycolactone inhibits SEC61-dependent co-translational translocation of proteins into endoplasmic reticulum resultant cytosolic translation triggers degradation mislocalized by ubiquitin-proteasome system. Inhibition SEC61 mycolactone also activates multiple EIF2S1/eIF2α kinases in integrated stress response (ISR). Here we show increased canonical...
Abstract Haemanthus coccineus extracts ( HCE ) have traditionally been used to treat a variety of diseases, like febrile colds or asthma. Since new therapeutic options against inflammatory processes are still urgently needed, we aimed pharmacologically characterise the anti‐inflammatory potential in vitro and vivo identify underlying bioactive component(s). The action on oedema formation leucocyte infiltration were analysed two murine models inflammation (dermal induced by arachidonic acid...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically-evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on primary endothelial cells vitro and vivo . show that mycolactone-induced changes morphology, adhesion, migration, permeability are dependent at Sec61...
Abstract The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically-evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on primary endothelial cells vitro and vivo . show that mycolactone-induced changes morphology, adhesion, migration, permeability are dependent at Sec61...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically-evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on primary endothelial cells vitro and vivo . show that mycolactone-induced changes morphology, adhesion, migration, permeability are dependent at Sec61...
Abstract The neglected tropical disease Buruli ulcer, caused by Mycobacterium ulcerans infection, displays coagulative necrosis in affected skin tissues. We previously demonstrated that exposure to the M. exotoxin mycolactone depletes expression of thrombomodulin and impacts anticoagulation at endothelial cell surface. Moreover, while widespread fibrin deposition is a common feature BU lesions, cause this phenotype not clear. Here, we performed sequential staining serial tissue sections...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone's effects on human primary endothelial cells vitro. show that mycolactone-induced changes morphology, adhesion, migration, and permeability are dependent at Sec61...