Search results for "Calcineurin"
showing 10 items of 40 documents
NFATc1 releases BCL6-dependent repression of CCR2 agonist expression in peritoneal macrophages fromSaccharomyces cerevisiaeinfected mice
2016
The link between the extensive usage of calcineurin (CN) inhibitors cyclosporin A and tacrolimus (FK506) in transplantation medicine and the increasing rate of opportunistic infections within this segment of patients is alarming. Currently, how peritoneal infections are favored by these drugs, which impair the activity of several signaling pathways including the Ca(++) /CN/NFAT, Ca(++) /CN/cofilin, Ca(++) /CN/BAD, and NF-κB networks, is unknown. Here, we show that Saccharomyces cerevisiae infection of peritoneal resident macrophages triggers the transient nuclear translocation of NFATc1β isoforms, resulting in a coordinated, CN-dependent induction of the Ccl2, Ccl7, and Ccl12 genes, all enc…
Fast Regulation of GABAAR Diffusion Dynamics by Nogo-A Signaling.
2019
Summary: Precisely controlling the excitatory and inhibitory balance is crucial for the stability and information-processing ability of neuronal networks. However, the molecular mechanisms maintaining this balance during ongoing sensory experiences are largely unclear. We show that Nogo-A signaling reciprocally regulates excitatory and inhibitory transmission. Loss of function for Nogo-A signaling through S1PR2 rapidly increases GABAAR diffusion, thereby decreasing their number at synaptic sites and the amplitude of GABAergic mIPSCs at CA3 hippocampal neurons. This increase in GABAAR diffusion rate is correlated with an increase in Ca2+ influx and requires the calcineurin-mediated dephospho…
Increased basal antioxidant levels in RCAN1 - deficient mice lowers oxidative injury after acute paraquat insult.
2020
RCAN1 is an inhibitor of the phosphatase calcineurin, which is involved in the regulation of oxidative stress and apoptosis, among other important cell processes. Here we have used RCAN1 deficient mice (RCAN1-/-) to elucidate its role after an acute oxidative insult such as paraquat injection. We have observed that RCAN1-/- mice show less oxidative damage than wildtype (WT) mice after treatment. Under basal conditions, RCAN1-/- animals express more calcineurin, heme oxygenase-1, Nrf2, and catalase compared to WT mice (controls). This may explain the less severe effect of paraquat treatment on RCAN1-/- mice compared to WT. We showed that oxidative stress is involved in the early stages of ap…
The Antiviral Properties of Cyclosporine. Focus on Coronavirus, Hepatitis C Virus, Influenza Virus, and Human Immunodeficiency Virus Infections
2020
This review updates current knowledge regarding the risk of viral infections, including COVID-19, in patients treated with cyclosporine. We also shortly refer to bacterial infections and parasitic infestations in patients treated with cyclosporin. Cyclosporine is an immunosuppressive drug, which is widely used in medicine, including in the treatment of autoimmune skin diseases in dermatology, rheumatology, ophthalmology and nephrology, and in organ transplantation. A usual concern associated with immunosuppressive treatment is the potential risk of infections. Interestingly, several data indicate a relatively low risk of infections, especially viral infections, in patients receiving cyclosp…
Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in…
2019
Background and purpose Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Experimental approach We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohis…
Association of SNPs with the efficacy and safety of immunosuppressant therapy after heart transplantation.
2015
Aim: Studying the possible influence of SNPs on efficacy and safety of calcineurin inhibitors upon heart transplantation. Materials & methods: In 60 heart transplant patients treated with tacrolimus or cyclosporine, we studied a panel of 36 SNPs correlated with a series of clinical parameters during the first post-transplantation year. Results: The presence of serious infections was correlated to ABCB1 rs1128503 (p = 0.012), CC genotype reduced the probability of infections being also associated with lower blood cyclosporine concentrations. Lower renal function levels were found in patients with rs9282564 AG (p = 0.003), related to higher blood cyclosporine blood levels. A tendency tow…
Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Res…
2010
Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neut…
Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus.
2008
Background Oral lichen planus (OLP) is considered to be an autoimmune disease of unknown aetiology that affects the mucosae, especially the oral cavity. Objective We compared tacrolimus 0.1% ointment and clobetasol 0.05% ointment for the treatment of OLP. Patients and methods A total of 32 patients (20 females and 12 males; all white, Italian origin, mean age of 43.6+/-18.4 years; 16 patients per treatment group) were treated with tacrolimus or clobetasol ointment for 4 weeks in a randomized, double-blind, clinical trial. Pain severity, burning sensation, and mucosal lesion extension were assessed using a four-point scale. Results At the end of the treatment period, symptom scores were sign…
Two yr mycophenolate mofetil plus low-dose calcineurin inhibitor for renal dysfunction after liver transplant
2009
We assessed the efficacy and outcome of low through level of calcineurin inhibitors (CNI) and introducing mycophenolate mofetil (MMF) in liver transplant (LT) patients with CNI-related renal dysfunction. Thirty LT patients were converted to combined therapy and compared with 30 patients used as a contemporary control group receiving CNI only. The two groups were matched for sex, age, months after LT, immunosuppressive treatment, creatinine level, presence of diabetes and calculated glomerular filtration rate (GFR) via Cockroft-Gault method. After two years, in the MMF serum creatinine decreased from 1.65 mg/dL (range 1.33-3.5) to 1.4 mg/dL (range 0.9-4.7) (p = 0.002) and GFR increased from …
Treatment of cutaneous lupus erythematosus: current practice variations
2015
The treatment of cutaneous lupus erythematous (CLE) remains a challenge. Most of the therapeutic options used in CLE have not been tested in randomized controlled studies and to date no agent has been approved. Therefore, CLE treatment is mostly based on personal experience. To better characterize therapeutic habits among physicians treating CLE patients, a questionnaire-based study about various aspects of topical and systemic treatment for CLE has been performed. The questionnaire was distributed among CLE experts, mostly from Japan, the USA, and Europe. A total of 82 completed questionnaires were assessed. High-potent and potent corticosteroids as well as calcineurin inhibitors were the…