A5043525120- Chemokine receptors and signaling
- Extracellular vesicles in disease
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Inflammatory mediators and NSAID effects
- Multiple Myeloma Research and Treatments
- Cancer Treatment and Pharmacology
- Ion Channels and Receptors
- Nerve injury and regeneration
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytokine Signaling Pathways and Interactions
- Complement system in diseases
- Asthma and respiratory diseases
- Pharmacological Effects of Natural Compounds
- Biochemical effects in animals
- Immune Response and Inflammation
- Cancer, Stress, Anesthesia, and Immune Response
- Adipose Tissue and Metabolism
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Osteoarthritis Treatment and Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Glycation End Products research
- Cancer Cells and Metastasis
IBSA Farmaceutici (Italy)
2015-2025
Dompé (Italy)
2015-2025
Laboratorios Farmaceúticos Rovi (Spain)
2024
Farmaceutici Damor (Italy)
2022
Lund University
2015
University of Naples Federico II
2015
Axxam (Italy)
2015
Linköping University
2015
IRCCS Ospedale San Raffaele
2015
Vita-Salute San Raffaele University
2015
ELR+ CXC chemokines are heparin-binding cytokines signalling through the CXCR1 and CXCR2 receptors. have been associated with inflammatory arthritis due to their capacity attract cells. Here, we describe an unsuspected physiological function of these molecules in articular cartilage homeostasis.Chemokine receptors ligands were detected by immunohistochemistry, western blotting RT-PCR. Osteoarthritis was induced wild-type CXCR2(-/-) mice destabilisation medial meniscus (DMM). CXCR1/2...
Osteosarcoma (OS), a malignant tumor of bone, kills through aggressive metastatic spread almost exclusively to the lung. Mechanisms driving this tropism for lung tissue remain unknown, though likely invoke specific interactions between cells and other within niche. Aberrant overexpression ΔNp63 in OS directly drives production IL-6 CXCL8. All these factors were expressed at higher levels metastases than matched primary tumors from same patients. Expression cell lines correlated strongly with...
Significance Persistent pain in inflammatory and neuropathic conditions is often refractory to conventional analgesic therapy, with most patients suffering unrelieved serious treatment-related side effects. There still a tremendous need identify novel therapeutics for control innovative biological mechanisms minimal In this paper we challenge the hypothesis that conserved structural motif across G protein-coupled receptor family plays regulatory role negative modulation of activation use...
In breast cancer it has been proposed that the presence of stem cells may drive tumor initiation, progression and recurrences. IL-8, up-regulated in cancer, associated with poor prognosis, increases CSC self-renewal cell line models. It signals via two surface receptors, CXCR1 CXCR2. Recently, IL-8/CXCR1 axis was as an attractive pathway for design specific therapies against cells. Reparixin, a powerful inhibitor, effective reducing vivo tumour-initiating population several NOD/SCID mice...
RATIONALE: Increased IL-8 levels and neutrophil accumulation in the airways are common features found patients affected by pulmonary diseases such as Asthma, Idiopathic Pulmonary Fibrosis, Influenza-A infection COPD. Chronic neutrophilic inflammation is usually corticosteroid insensitive may be relevant progression of those diseases. OBJECTIVE: To explore role Ladarixin, a dual CXCR1/2 antagonist, several mouse models airway with significant component. FINDINGS: Ladarixin was able to reduce...
Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which challenging to treat. Several distinct classes drugs are currently used for the treatment chronic NP, but each drug targets only narrow components underlying pathophysiological mechanisms, bears limited efficacy, comes with dose-limiting side effects. Multimodal therapies have been proposed as potential therapeutic approaches target multiple mechanisms nociceptive transmission modulation....
Abstract Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage human ulcerative colitis (UC). Ligands of CXC chemokine receptor 1 2 (CXCR1/R2) chemoattractants PMN, high levels were found the UC patients. To investigate pathophysiological played by CXCR2 experimental UC, we induced chronic WT CXCR2−/− mice two consecutive cycles 4% dextran sulfate sodium administration drinking water. In wild-type (WT) mice,...
Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents frequent and serious consequence chemotherapy agents. Over the last years, significant progress has been achieved in elucidating underlying pathogenesis CIPN. The interference taxanes with microtubule proposed as mechanism leads to altered axonal transport permanent neurological damages. inflammatory process activated by chemotherapeutic agents considered potential trigger nociceptive CIPN.In this...
Rationale: Influenza A infections are a leading cause of morbidity and mortality worldwide especially when associated with secondary pneumococcal infections. Inflammation is important to control pathogen proliferation but may also tissue injury death. CXCR1/2 chemokine receptors relevant for the recruitment neutrophils. We investigated role during influenza, post-influenza Methods: Mice were infected influenza virus (IAV) or Streptococcus pneumoniae then treated daily antagonist DF2162. To...
Methionine is an aliphatic, sulfur-containing, essential amino acid that has been demonstrated to have crucial roles in metabolism, innate immunity, and activation of endogenous antioxidant enzymes, including methionine sulfoxide reductase A/B the biosynthesis glutathione counteract oxidative stress. Still, restriction avoids altered methionine/transmethylation thus reducing DNA damage possibly avoiding neurodegenerative processes. In this study, we wanted study preventive effects...
Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved pathophysiology. signaling increased locally lung, especially neutrophils of critically ill patients...
Background and Purpose Transient receptor potential (TRP) channels are a superfamily of non‐selective cation permeable involved in peripheral sensory signalling. Animal studies have shown that several TRPs important players pain modulation. Among them, the TRP melastatin 8 (TRPM8) has elicited more interest for its controversial role nociception. This channel, expressed by subpopulation neurons dorsal root ganglia (DRG) trigeminal (TG), is activated cold temperatures cooling agents. In...
Abstract Interleukin-8 (IL-8), the prototype of α (i.e., C-X-C branch) chemokine family, induced elastase release in a concentration-dependent manner (50-1000 ng/mL) cytochalasin B-treated human polymorphonuclear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin-1β (IL-1β) at concentrations that by themselves inactive. The effect IL-1β clearly observed after 5 min and maximal 30-min preincubation cells. present over whole active...
Abstract Transient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it activated by temperatures cooling compounds, such as menthol icilin. Because of its role in allodynia, hyperalgesia painful syndromes TRPM8 antagonists are currently being pursued therapeutic agents for treatment pain hypersensitivity. Recently has been found subsets bladder sensory nerve fibres, providing an opportunity to understand...
The central nervous system (CNS) constitutively expresses complement (C) membrane receptors and proteins, including the component C5a. This is a crucial terminal effector of C cascade, mostly involved in pain neuroinflammatory conditions. Aberrant activation C5a protein its receptor C5aR has been reported to play critical role neurodegenerative diseases, with important clinical consequences. Here we have investigated effects DF3016A, novel selective antagonist, able penetrate blood-brain...
CXCL1, a functional murine orthologue of the human chemokine CXCL8 (IL-8), and its CXCR1 CXCR2 receptors were investigated in model acquired epilepsy developing following status epilepticus (SE) induced by intra-amygdala kainate. also studied temporal lobe (TLE). The involvement seizure generation neuronal cell loss was assessed mice using reparixin (formerly referred to as repertaxin), non-competitive allosteric inhibitor CXCR1/2 receptors. We found significant increase hippocampal CXCL1...
Chronic pain is an enormous public health concern, and its treatment still unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin treatment, we sought to combine ketoprofen lysine salt (KLS) obtain effective multimodal therapeutic approach for chronic pain. Using relevant vitro models, first demonstrated that KLS have supra-additive modulating key pathways neuropathic gastric mucosal damage. To...
Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of several anti-neoplastics and main cause sensory disturbances in cancer survivors, negatively impacting patients’ quality life. Peripheral nerve degeneration or small fibre generally accepted as the underlying mechanism development CIPN. Recent evidence has contributed to clarify determinant role cytokines chemokines process leading neuronal hyperexcitability. Exposure oxaliplatin triggers...
The activation of CXCR1/2 has been implicated in the genesis inflammatory and postoperative pain. Here, we investigated a novel orally acting allosteric inhibitor (DF2755A) evaluated its antinociceptive effect several models post-operatory DF2755A was tested vitro for efficacy chemotaxis assay, selectivity toxicity. In vivo, C57Bl/6 mice were treated with following experiments performed: pharmacokinetic profile; hyperalgesia using electronic pressure meter test; neutrophil migration assay...
Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent impairing side effects of antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind activate complement component 5a receptor 1 (C5aR1) this binding is crucial in etiology paclitaxel-induced CIPN anaphylaxis. Starting from our previous data demonstrating role interleukin (IL)-8 neuronal toxicity, searched for proteins IL-8 expression and, by using...
The intestinal barrier is the main contributor to gut homeostasis. Perturbations of epithelium or supporting factors can lead development hyperpermeability, termed “leaky gut”. A leaky characterized by loss epithelial integrity and reduced function barrier, associated with prolonged use Non-Steroidal Anti-Inflammatories. harmful effect NSAIDs on gastric considered an adverse that common all drugs belonging this class, it strictly dependent NSAID properties inhibit cyclo-oxygenase enzymes....
Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXCR1/2 receptors, elevated in the serum of patients with Temporal Lobe Epilepsy (TLE). Its murine ortholog CXCL1, implicated seizure generation and neuronal loss. This study evaluates anti-epileptogenic anti-seizure effect reparixin, an allosteric antagonist amygdaloid kindling rat model TLE. Reparixin was administered via osmotic pumps (8mg/kg/h) during period over 14 days seizures induced twice daily by...