• Title/Summary/Keyword: calcineurin inhibitors

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The safety, immunological benefits, and efficacy of ginseng in organ transplantation

  • Lim, Sun Woo;Luo, Kang;Quan, Yi;Cui, Sheng;Shin, Yoo Jin;Ko, Eun Jeong;Chung, Byung Ha;Yang, Chul Woo
    • Journal of Ginseng Research
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    • v.44 no.3
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    • pp.399-404
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    • 2020
  • Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

Immunosuppressive Properties of Catfish Bile from Silurus asotus: Inhibition of T Cell Activation in Mouse Splenocytes

  • Joo, Seong-Soo
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.598-602
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    • 2008
  • Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.

Tacrolimus and cyclosporine A inhibit both class I-restricted presentation pathway and class II- restricted presentation pathway of exogenous antigen.

  • Yang, In-Ho;Lee, Young-Ran;Kim, Hyeon-Seon;Lee, Jae-Kwon;Im, Sun-A;Li, Hong;Han , Kun;Song, Suk-Gil;Lee, Chong-Kil
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.306.2-306.2
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    • 2002
  • The main targets for the immunosuppressive calcineurin inhibitors. tacrolimus (FK-506) and cyclosporine A (CsA). have been considered to be activated T cells. but not antigen presenting cells (APCs). In the present study. we examined the effects of these drugs on the MHC-restricted presentation of exogenously added antigen. ovalbumin (OVA). in dendritic cells (DCs). Particulate form of OVA was efficiently captured. processed and presented on class I MHC molecules (cross-presentation) as well as on class II MHC molecules. (omitted)

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Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro

  • Xu, Ping;Chen, Jie;Tan, Cheng;Lai, Ren-Sheng;Min, Zhong-Sheng
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.287-292
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    • 2017
  • Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, $10^2$nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, $10^2$ and $10^3nM$ significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to $10^2$nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at $10^2nM$. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

T-lymphocyte Inactivation and Anti-atopic Effects of Diarylheptanoid Hirsutenone Isolated from Alnus japonica (오리나무유래 디아릴헵타노이드 허수테논의 T 세포활성억제 및 항아토피 효능연구)

  • Lee, Do Ik;Seo, Seong Jun;Joo, Seong Soo
    • Korean Journal of Food Science and Technology
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    • v.45 no.4
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    • pp.508-514
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    • 2013
  • 2Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However, it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model. Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation, similar to INCA-6.

Research Trends on Compounds that Promote Melanin Production Related to Hair Graying (모발 백발화와 관련된 melanin 생성을 촉진시키는 화합물의 연구동향)

  • Moon-Moo Kim
    • Journal of Life Science
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    • v.33 no.5
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    • pp.445-454
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    • 2023
  • Hair graying is the result of a malfunction in the signaling pathways that control melanogenesis, and it is activated by UV light, melanocyte-stimulating hormone (MSH), stem cell factor (SCF), Wnt, and endothelin-1 (ET-1). To prevent hair graying, synthetic and natural compounds can be used to stimulate melanogenesis effectively under the control of tyrosinase, tyrosine hydroxylase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF). This article describes a crucial strategy to resolve the problem of hair graying, as well as recent advances in the signaling pathway related to melanogenesis and hair graying. In particular, the article reviews potentially effective therapeutic agents that promote melanogenesis, such as antioxidants that modulate catalase, methionine sulfoxide reductase, and sirtuin 1 (SIRT1) activators including resveratrol, fisetin, quercetin, and ginsenoside. It also discusses vitiligo inhibitors, such as corticosteroids, calcineurin inhibitors, and palmitic acid methyl ester, as well as activators of telomerase expression and activity, including estrogen, androgen, progesterone, and dihydrotestosterone. Furthermore, it explores compounds that can inhibit hair graying, such as latanoprost, erlotinib, imatinib, tamoxifen, and levodopa. In conclusion, this article focuses on recent research trends on compounds that promote melanin production related to hair graying.

Medicinal potential of Panax ginseng and its ginsenosides in atopic dermatitis treatment

  • Lorz, Laura Rojas;Kim, Mi-Yeon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.8-13
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    • 2020
  • Atopic dermatitis (AD) is a chronic and relapsing inflammatory disease that affects 1%-20% of people worldwide. Despite affecting many people, AD current treatments, such as corticosteroids and calcineurin inhibitors, have not only harmful secondary effects but are also often ineffective. Therefore, natural nontoxic compounds are on high demand for developing new effective AD treatments. Panax ginseng Meyer has been used traditionally for its promising healing and restorative properties to treat many diseases including skin disorders, reason why in this review we want to explore the research performed with AD and P. ginseng as well as determining its potential for new drug development. Previous researches have shown that P. ginseng has positive effects in AD patients such as lower eczema area and severity index, transepidermal water loss, and immunoglobulin E levels and better quality of sleep. In vivo animal models, as well, have shown positive results to P. ginseng and derived ginsenosides, such as the decrease of transepidermal water loss, immunoglobulin E levels in serum, allergy-related cytokines, and downregulation of NF-κB, MAPK, and Ikaros pathways. All of these previous data suggest that P. ginseng and its derived ginsenosides are undoubtedly a nontoxic effective option to treat AD.

Case Report of a Pilot with Atopic Dermatitis (아토피성 피부염을 가진 조종사의 판정 증례보고)

  • Kwon, Young Hwan
    • Korean journal of aerospace and environmental medicine
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    • v.31 no.2
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    • pp.54-56
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    • 2021
  • Atopic dermatitis is a condition that makes skin red and itchy. It is common in children but can occur at any age. Atopic dermatitis is chronic and tends to flare periodically. The pathogenesis of the disease has not yet been clearly elucidated but genetic predisposition, immunological dysfunction, and environmental factors are presumed to be involved in the pathogenesis. In general, it is difficult to cure, but as time passes, most of them heal naturally and the symptoms disappear, but the symptoms continue to recur. So, the basic treatment is to relieve the pruritus and prevent it from reoccurring. Treatment involves avoiding things that make the condition worse, daily bathing with application of moisturizing cream afterwards, applying steroid creams when flares occur, and medications to relieve itching sensation. Steroid pills or creams based on calcineurin inhibitors may occasionally be used if other measures are not effective. When examining a pilot with atopic dermatitis, the dermatitis condition, the treatment being used, and the side effects of the medications should be considered. This case involves an otherwise healthy applicant for the 1st class medical certification who has had atopic dermatitis.

Human Skin Safety Test of Green Tea Cell Extracts in Condition of Allergic Contact Dermatitis

  • Kim, Hyun-Kyu;Choi, Sun-Young;Chang, Hui-Kyoung;Baek, Seok-Yun;Chung, Jin-Oh;Rha, Chan-Su;Kim, Beom-Joon;Kim, Myeung-Nam
    • Toxicological Research
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    • v.28 no.2
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    • pp.113-116
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    • 2012
  • Various kinds of positive effects of green tea extracts had been studied for long time which included anti-inflammation, anti-aging, and cardiometabolic effects. Although topical steroid and non-steroidal calcineurin inhibitors may control clinical symptoms of allergic contact dermatitis, some of patients also present allergic reaction to these topical agents. Therefore, we have tried green tea extracts for managing this skin disorder with expectation of anti-inflammatory effect without potential side effects including skin irritation and toxic responses. The toxicity test of green tea extract also did not show any sign of irritation in the skin throughout the test period. Moderate severity of allergic contact dermatitis presented satisfactory clinical outcome at second week follow-up which was final visit of outpatient. This result mean that green tea extract has a positive effect for managing allergic contact dermatitis but its potency and efficacy seem to be so not strong enough to control moderate severity allergy skin lesion. In this pilot study, we were able to conclude that green tea cell extracts might be applied for potential anti-inflammatory soaking without skin toxicity.

Signaling Through the Murine T Cell Receptor Induces IL-17 Production in the Absence of Costimulation, IL-23 or Dendritic Cells

  • Liu, Xikui K.;Clements, James L.;Gaffen, Sarah L.
    • Molecules and Cells
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    • v.20 no.3
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    • pp.339-347
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    • 2005
  • IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.