A5089029249- Receptor Mechanisms and Signaling
- Asthma and respiratory diseases
- Mast cells and histamine
- Phosphodiesterase function and regulation
- Cardiac electrophysiology and arrhythmias
- Livestock and Poultry Management
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- Ion channel regulation and function
- Cell Adhesion Molecules Research
- Neuropeptides and Animal Physiology
- Parasite Biology and Host Interactions
- Urticaria and Related Conditions
- Helminth infection and control
- Nitric Oxide and Endothelin Effects
- Gut microbiota and health
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Ion Channels and Receptors
- Renin-Angiotensin System Studies
- Forensic Entomology and Diptera Studies
- T-cell and B-cell Immunology
- Allergic Rhinitis and Sensitization
- Rabbits: Nutrition, Reproduction, Health
- Heart Failure Treatment and Management
University Medical Center Hamburg-Eppendorf
2015-2024
Universität Hamburg
2015-2024
German Centre for Cardiovascular Research
2017-2024
Imperial College London
2023
Jawaharlal Institute of Post Graduate Medical Education and Research
2022
Michigan State University
2017-2021
University of Pennsylvania
2010-2017
University of Würzburg
2013-2016
University Medical Center of the Johannes Gutenberg University Mainz
2015
Johannes Gutenberg University Mainz
2015
Human LL-37 is a multifunctional antimicrobial peptide that promotes inflammation, angiogenesis, wound healing, and tumor metastasis. Most effects of are mediated via the activation cell surface G protein-coupled receptor FPR2 on leukocytes endothelial cells. Although induces chemotaxis, degranulation, chemokine production in mast cells, involved mechanism its regulation remain unknown. MrgX2 member Mas-related genes primarily expressed human dorsal root ganglia We found line LAD2 CD34+...
Human β-defensins (hBDs) stimulate degranulation in rat peritoneal mast cells vitro and cause increased vascular permeability rats vivo. In this study, we sought to determine whether hBDs activate murine human delineate the mechanisms of their regulation. hBD2 hBD3 did not induce or bone marrow-derived (BMMC) had no effect on By contrast, these peptides induced sustained Ca(2+) mobilization substantial cells, with being more potent. Pertussis toxin (PTx) hBD-induced mobilization, but La(3+)...
Human mast cells express the G protein coupled receptor (GPCR) for C5a (CD88). Previous studies indicated that could cause cell degranulation, at least in part, via a mechanism similar to proposed basic neuropeptides such as substance P, possibly involving Mas-related gene 2 (MrgX2). We therefore sought more clearly define specificity C5a-induced degranulation. found LAD2, human line, and CD34<sup>+</sup> cell-derived primary functional MrgX1 MrgX2 but immature line HMC-1 does not. A potent...
Mast cells are tissue resident innate immune known for their prominent role in mediating allergic reactions. MAS-related G-protein coupled receptor-X2 (MRGPRX2) is a promiscuous receptor (GPCR) expressed on mast that activated by several ligands share cationic and amphipathic properties. Interestingly MRGPRX2 include certain FDA-approved drugs, antimicrobial peptides neuropeptides. Consequently, this has been implicated causing cell-dependent pseudo-allergic reactions to these drugs chronic...
Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during cell receptor (TCR)-mediated sensing phosphoantigens (PAg) derived from microbes tumors. However, molecular rules governing PAg remain largely unknown. Here, we establish three mechanistic principles PAg-mediated γδ activation. First, in humans, following binding to intracellular BTN3A1-B30.2 domain, TCR triggering involves extracellular V-domain BTN3A2/BTN3A3. Moreover, localization both protein...
Abstract Aims Gene therapy with cardiac phosphodiesterases (PDEs), such as phosphodiesterase 4B (PDE4B), has recently been described to effectively prevent heart failure (HF) in mice. However, exact molecular mechanisms of its beneficial effects, apart from general lowering cardiomyocyte cyclic adenosine monophosphate (cAMP) levels, have not elucidated. Here, we studied whether gene two types PDEs, namely PDE2A and PDE4B, can pressure-overload-induced HF mice by acting on restoring altered...
Abstract Natriuretic peptides (NPs) are important hormones that regulate multiple cellular functions including cardiovascular physiology. In the heart, two natriuretic peptide receptors NPR1 and NPR2 act as membrane guanylyl cyclases to produce 3′,5′-cyclic guanosine monophosphate (cGMP). Although both protect from cardiac hypertrophy, their effects on contractility markedly different, little effect (NPR1) pronounced negative inotropic positive lusitropic responses (NPR2) with unclear...
[Figure: see text].
Background: The sarcoplasmic reticulum (SR) Ca 2+ -ATPase 2 (SERCA2) mediates reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) release from triggers contraction. /CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation PLN (phospholamban) RYR direct phosphorylation. However, mechanisms for CaMKIIδ anchoring to SERCA2-PLN its regulation by local signals remain elusive. objective this study...
Chronic neuroinflammation is a consequence of disease pathogenesis underlying neurological disorders at large. While the immune response that triggers inflammatory signaling cascades unresolved, its progression could cause functional damage to neurons and glial cells, including astrocytes, microglia, oligodendrocytes. Controlling neuroinflammatory early stage critical prevent irreversible tissue necrosis. application anti-inflammatory drugs standard practice, their protracted use known...
The complement component C3a induces degranulation in human mast cells via the activation of cell surface G protein coupled receptors (GPCR; C3aR). For most GPCRs, agonist-induced receptor phosphorylation leads to recruitment β-arrestin-1/β-arrestin-2; resulting desensitization and internalization. Activation GPCRs also ERK1/2 two temporally distinct pathways; an early response that reflects a delayed is independent but requires β-arrestins. role β-arrestins on C3aR activation/regulation...
Background The complement component C3a activates human mast cells via its cell surface G protein coupled receptor (GPCR) C3aR. For most GPCRs, agonist-induced phosphorylation leads to desensitization, internalization as well activation of downstream signaling pathways such ERK1/2 phosphorylation. Previous studies in transfected COS overexpressing kinases (GRKs) demonstrated that GRK2, GRK3, GRK5 and GRK6 participate C3aR However, the roles these GRKs on regulation mediator release remain...
// Kshitij Gupta 1 , Akhil Kotian 2 Hariharan Subramanian Henry Daniell and Hydar Ali Department of Pathology, School Dental Medicine, University Pennsylvania, Philadelphia, PA, USA Biochemistry, Correspondence to: Ali, email: Daniell, Keywords : antimicrobial peptides, mast cells, retrocyclin, protegrin, chloroplast, MrgX2, Immunology Microbiology Section, Immune response, Immunity Received July 04, 2015 Accepted August 30, Published September 10, Abstract Preclinical evaluation...
Human β-defensin3 (hBD3) and the cathelicidin LL-37 are host defense peptides (HDPs) that directly kill microbes display immunomodulatory/wound-healing properties via activation of chemokine, formylpeptide epidermal growth factor receptors on leukocytes epithelial cells. A C-terminal 14 amino acid hBD3 peptide with all Cys residues replaced Ser (CHRG01) an consisting 17-29 (FK-13) antimicrobial activity but lack immunomodulatory property. Surprisingly, we found CHRG01 FK-13 caused Ca 2+...
Mast cells are inflammatory immune that play an essential role in mediating allergic reactions humans. It is well known mast cell activation critically regulated by intracellular calcium ion (Ca2+) concentrations. MAS-related G-protein coupled receptor-X2 (MRGPRX2) a receptor (GPCR) expressed on activated various ligands, including several FDA approved drugs; consequently, this has been implicated causing pseudo-allergic MRGPRX2 leads to increase Ca2+ levels; however, the mobilizing...
L-selectin functions as an important adhesion molecule that mediates tethering and rolling of lymphocytes by binding to high endothelial venule (HEV)-expressed ligands during recirculation. Subsequent lymphocyte arrest transmigration require activation through HEV-decorated homeostatic chemokines such secondary lymphoid tissue chemokine (SLC; CCL21) its counterreceptor, CCR7. Importantly, also a signaling molecule. In this study, induced ligation using mAb or cell-expressed ligand...
The ubiquitous second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling (ECC) by signaling in discrete subcellular microdomains. Phosphodiesterase subfamilies 4B and 4D are critically involved the regulation of cAMP mammalian cardiomyocytes. Alterations PDE4 activity human hearts has been shown to result arrhythmias heart failure. Here, we sought systematically investigate specific roles PDE4B PDE4D dynamics three distinct microdomains,...
Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment several cardiovascular diseases. The sGC stimulator riociguat has been approved two forms pulmonary hypertension. Platelets contain large amounts and play key role in regulation haemostasis. Therefore, we investigated effects on platelet function.The effect human activation aggregation was investigated. sGC-specific were determined by comparing wild-type platelet-specific sGC-knockout...
Chemotherapy-induced thrombocytopenia is a common bleeding risk in cancer patients and limits chemotherapy dose frequency. Recent data from mouse human platelets revealed that activation of protein kinase A/G (PKA/PKG) not only inhibited thrombin/convulxin-induced platelet but also prevented the pro-coagulant state. Here we investigated whether or PKA/PKG could attenuate caspase-dependent apoptosis induced by anti-cancer drugs ABT-737 (the precursor navitoclax) thymoquinone (TQ), thereby...