0000000000162007
AUTHOR
Kurt Lucas
Nanoscale distribution of TLR4 on primary human macrophages stimulated with LPS and ATI
Toll-like receptor 4 (TLR4) plays a crucial role in the recognition of invading pathogens. Upon activation by lipopolysaccharides (LPS), TLR4 is recruited into specific membrane domains and dimerizes. In addition to LPS, TLR4 can be stimulated by wheat amylase-trypsin inhibitors (ATI). ATI are proteins associated with gluten containing grains, whose ingestion promotes intestinal and extraintestinal inflammation. However, the effect of ATI vs. LPS on the membrane distribution of TLR4 at the nanoscale has not been analyzed. In this study, we investigated the effect of LPS and ATI stimulation on the membrane distribution of TLR4 in primary human macrophages using single molecule localization m…
Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects.
Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to dif…
Aerosol Health Effects from Molecular to Global Scales.
Poor air quality is globally the largest environmental health risk. Epidemiological studies have uncovered clear relationships of gaseous pollutants and particulate matter (PM) with adverse health outcomes, including mortality by cardiovascular and respiratory diseases. Studies of health impacts by aerosols are highly multidisciplinary with a broad range of scales in space and time. We assess recent advances and future challenges regarding aerosol effects on health from molecular to global scales through epidemiological studies, field measurements, health-related properties of PM, and multiphase interactions of oxidants and PM upon respiratory deposition. Global modeling combined with epide…
Cinnamon extract inhibits allergen-specific immune responses in human and murine allergy models.
Background Ceylon cinnamon has been shown to possess anti-inflammatory properties in many diseases including allergic inflammation. Objective The aim of this study was to analyse in more detail the effects of cinnamon extract (CE) and its major compounds p-cymene and trans-cinnamaldehyde (CA) on allergen-specific immune responses in vitro and in vivo. Methods Therefore, monocyte-derived mature dendritic cells (DC) from grass or birch pollen allergic donors were pulsed with the respective allergen in the presence or absence of CE, p-cymene, CA or the solvent ethanol and co-cultured with autologous CD4+ T cells. Furthermore, basophil activation test was performed with or without CE or ethanol…
Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential
Amylase trypsin inhibitors (ATI) can be found in all gluten containing cereals and are, therefore, ingredient of basic foods like bread or pasta. In the gut ATI can mediate innate immunity via activation of the Toll-like receptor 4 (TLR4) on immune cells residing in the lamina propria, promoting intestinal, as well as extra-intestinal, inflammation. Inflammatory conditions can induce formation of peroxynitrite (ONOO-) and, thereby, endogenous protein nitration in the body. Moreover, air pollutants like ozone (O3) and nitrogen dioxide (NO2) can cause exogenous protein nitration in the environment. Both reaction pathways may lead to the nitration of ATI. To investigate if and how nitration mo…
Molecular hydrogen (H 2 ) as a potential treatment for acute and chronic fatigue
Many diseases as well as acute conditions can lead to fatigue, which can be either temporary or chronic in nature. Acute fatigue develops frequently after physical exercise or after alcohol hangover, whereas microbial infections such as influenza or COVID-19 and chronic diseases like Parkinson's disease or multiple sclerosis are often associated with chronic fatigue. Oxidative stress and a resulting disturbance of mitochondrial function are likely to be common denominators for many forms of fatigue, and antioxidant treatments have been shown to be effective in alleviating the symptoms of fatigue. In this study, we review the role of reactive oxygen and nitrogen species in fatigue and the an…
Anti-inflammatory effects of cinnamon extract and identification of active compounds influencing the TLR2 and TLR4 signaling pathways
Purpose: Inflammatory processes are involved in many diseases. The bark of Cinnamomum verum and its extracts are well known for anti-inflammatory effects, but the underlying active compounds and chemical mechanisms are not yet fully identified. The objective of this study was to elucidate how cinnamon extract, specifically active compounds, and their combinations influence the signaling pathways of inflammation, especially through toll-like receptors TLR2 and TLR4. Methods: Bioassay-guided fractionation was performed for standard ethanolic cinnamon extract using high performance liquid chromatography followed by compound identification in the determined active fractions by high-resolution m…
Fresh water, marine and terrestrial cyanobacteria display distinct allergen characteristics.
During the last decades, global cyanobacteria biomass increased due to climate change as well as industrial usage for production of biofuels and food supplements. Thus, there is a need for thorough characterization of their potential health risks, including allergenicity. We therefore aimed to identify and characterize similarities in allergenic potential of cyanobacteria originating from the major ecological environments. Different cyanobacterial taxa were tested for immunoreactivity with IgE from allergic donors and non-allergic controls using immunoblot and ELISA. Moreover, mediator release from human FceR1-transfected rat basophilic leukemia (RBL) cells was measured, allowing in situ ex…
Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment
AbstractOvershooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate infla…