Transplantation
Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple in Basic Urological Sciences, 2021
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.
Immune system modulators
Gabriel Virella in Medical Immunology, 2019
Derived from the fungus Tolypocladium inflatum, cyclosporine A is a cyclic undecapeptide that works to selectively inhibit T lymphocytes by suppression of humoral T-cell dependent and cell-mediated responses. It binds to the cytosol-based protein cyclophilin to form a complex that goes on to bind to and inactivate calcineurin. Normally, calcineurin activates nuclear factor of activated T cells (NF-AT). NF-AT, in turn, upregulates expression of interleukin-2 (IL-2), a pro-inflammatory cytokine. The inactivation of calcineurin thus downregulates production of IL-2, as well as a number of other cytokines produced via the Ca2+ associated T-cell activation pathway, including IL-3, IL-4, interferon-γ (IFN-γ), and tumor necrosis factor (TNF). The predominant targets of cyclosporine are CD4+ helper T cells, but cyclosporine also impedes the differentiation of Foxp3T regulatory cells and also both directly and indirectly inhibits the activation of cytotoxic T-cell precursors.
Mucosal immune responses to microbes in genital tract
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in 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.
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.
Cyclophilin inhibition as a potential treatment for nonalcoholic steatohepatitis (NASH)
Published in Expert Opinion on Investigational Drugs, 2020
Daren R. Ure, Daniel J. Trepanier, Patrick R. Mayo, Robert T. Foster
We have described the primary ways in which the three best-known cyclophilin isoforms, cyclophilins A, B and D, participate in pathophysiological activities prevalent in NASH – dysregulated mitochondrial metabolism, mPT-mediated cell death, inflammatory cell recruitment and activation, and promotion of fibrotic collagen production and maturation. These activities are not unique to NASH or liver diseases; they have been studied in even greater detail in other organ systems and disorders. For example, most of the understanding of mPT has come from studies of ischemia-reperfusion injury in myocardial infarction. Cardiovascular disorders also have been most prominent in deciphering cyclophilin inflammatory activities. Neurological injury is an area of great interest as well. Moreover, fourteen other cyclophilin isoforms exist in the human proteome, suggesting many other regulatory roles. The broad functionality of prolyl isomerization is what links all these disparate activities.
Related Knowledge Centers
- Catalysis
- Ciclosporin
- Immunosuppressive Drug
- Isomerization
- Peptide Bond
- Proline
- Protein
- Transplant Rejection
- Organ Transplantation
- Prolyl Isomerase