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Transplantation
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Jonathon Olsburgh, Rhana H. Zakri
CiclosporinIsolated from Tolypocladium inflatum by Sandoz in 1970 in Basel, Switzerland.J.F. Borel discovered its immunosuppressive activity in 1976.First transplant use in humans by Sir Roy Calne in 1978.Binds with cyclophilin — an intracellular protein of the immunophilin family.Forms a complex that inhibits calcineurin.
Cellular and Molecular Interactions in the Induction of Inflammation in Rheumatic Diseases
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
The role of T cells in arthritis is clear, even though certain anticipated cytokines are absent within the synovium of patients. Although most forms of immunosuppressive therapy that benefit arthritis inhibit several aspects of immune function (1), specific inhibition of T cell function, in particular inhibition of lymphokine synthesis, ameliorates the disease process. In this regard, cyclosporin A (CsA), which acts specifically during T lymphocyte activation to inhibit the transcription of a limited set of early activation genes, including IL-2, IL-3, IFN-γ, TNF, and c-myc (92,93), effectively modulates the pathogenic events in certain subsets of rheumatoid arthritis patients (7). CsA binds to and inhibits cyclophilin, a peptidyl-prolyl isomerase responsbile for catalyzing the refolding of proteins and peptides into their native conformations during T cell activation (94,95). Comparison of high-dose (10 mg/kg) and low-dose (1 mg/kg) oral regimens in a prospective 6 month randomized, double-blind trial revealed that CsA significantly reduced disease activity by several parameters and improved function in a dose-related manner. Although drug-related toxicities occurred, these toxicities were often reversible with a reduction in the dose (7). These studies confirm the pivotal role of lymphocytes in the pathogenic process and point to additional related avenues of selective therapy.
Mucosal immune responses to microbes in genital tract
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Innate recognition of HIV-1 or retroviruses in general remains unclear. pDCs can produce IFN-α in response to HIV-1 through a process that likely involves TLR7 (Figure 21.2). In infected cells, HIV-1 viral RNA is reverse transcribed into viral cDNA, which is recognized by a cytosolic DNA sensor, cGAS. The host factor TREX1, an exonuclease, inhibits innate immune detection of HIV DNA by metabolizing nonproductive reverse transcription products. Innate immune response to HIV-1 in DCs depends on interaction between newly synthesized HIV-1 capsid and cellular cyclophilin A (Figure 21.3a). In addition, HIV-1 induces global disruption of the innate signaling pathway within infected cells by degrading IRF3, making directly infected cells incapable of IFN production.
Considerations of the effects of commonly investigated drugs for COVID-19 in the cholesterol synthesis pathway
Published in Expert Opinion on Pharmacotherapy, 2021
Juan Luis Gomez Marti, Adam M. Brufsky
Basigin (CD147) and Cyclophilin A (CyPA) are membrane receptors used by SARS-CoV. Basigin is a transmembrane glycosylated immunoglobulin and principal receptor of extracellular cyclophilins. Cyclophilins are a family of ubiquitously distributed chemotactic agents that mediate intracellular trafficking and signal conduction. These are released extracellularly during an inflammatory response and commonly exhibited by dying cells. CyPA is the most abundant cyclophilin isoform. The chemotactic effects of CyPA take place primarily after binding to the extracellular domain of basigin. Downstream signaling catalyzes matrix metalloprotease (MMP) release, facilitating leukocyte recruitment [7]. Basigin acts as a receptor for several viruses including measles, HIV-1 and SARS-CoV [8]. Viral binding to basigin induces CyP binding to the N protein of SARS-CoV virions, permitting cellular entry [9]. A preprint of preliminary results in a clinical trial has shown an association between anti-basigin antibodies and decreased hospitalization length and disease severity [10].
Combine colorants of tartrazine and erythrosine induce kidney injury: involvement of TNF-α gene, caspase-9 and KIM-1 gene expression and kidney functions indices
Published in Toxicology Mechanisms and Methods, 2021
Wopara Iheanyichukwu, Adebayo O. Adegoke, Olusegun G. Adebayo, Modo Emmanuel U., Aziemeola Pius Egelege, Jeremiah T. Gona, Fortune M. Orluwene
Cyclophilin is a cell-protector gene necessary for the maintenance of essential cellular functions. It can be found in both normal and diseased cells. Previous and recent studies have revealed that Cyclophilin is released by stimulus due to inflammation in several human diseased cells (Nigro et al. 2013). Repeated treatment with the combine tartrazine and erythrosine for 23 days showed increase in kidney pro-inflammatory cytokines gene expression. In kidney inflammation, TNF-α is secreted in significant amounts and is also seen to specifically intensify or provoke kidney disease progressions, slow down proper functioning and ultimately leads to the death of kidney cells (Tbahriti et al. 2013; Wu et al. 2017). The increase level of kidney pro-inflammatory cytokines precipitates cell degeneration leading to dysfunction, impairment or injury to the kidney and other nearby cells (Chen et al. 2018). The gene expression for TNF-α (2.5 mg/kg T+E, 5 mg/kg T+E and 20 mg/kg T+E) all shows significant up-regulation indicating a serious injury or inflammatory activities in the kidney of the treated rats. This finding aligns with previous work done on kidney inflammation following administration of toxic compounds or in acute/chronic renal failure (Tbahriti et al. 2013; Wu et al. 2017; Chen et al. 2018, 2019).
The intestinal quorum sensing 3-oxo-C12:2 Acyl homoserine lactone limits cytokine-induced tight junction disruption
Published in Tissue Barriers, 2020
Doriane Aguanno, Garance Coquant, Barbara G. Postal, Céline Osinski, Margaux Wieckowski, Daniel Stockholm, Jean-Pierre Grill, Véronique Carrière, Philippe Seksik, Sophie Thenet
Total RNA was extracted from Caco-2/TC7 cells using TRI Reagent (Molecular Research Center, Cincinnati, OH, USA) according to the manufacturer’s instructions. Reverse Transcription (RT) was performed with 1 μg RNA using a high-capacity complementary DNA (cDNA) reverse transcriptase kit (Applied Biosystem, Thermo Fisher Scientific). For claudin genes, as CLDN4 (claudin 4) has no intron, RT was performed with 0.5 µg of previously DNAse-treated RNA (Invitrogen™ Kit TURBO DNA-free). Semi-quantitative real-time PCR was performed with the Mx3000P Stratagene system using SYBR Green (Agilent, Les Ulis, France) according to the manufacturer’s procedures. Cyclophilin was used as the reference gene. After amplification, Ct were determined and relative gene expression was analyzed using the 2−ΔΔCt method. Sequences of the oligonucleotide primers used are reported in Table 1.