Cyclosporin A inhibits the early phase of NF-κB/RelA activation induced by CD28 costimulatory signaling to reduce the IL-2 expression in human peripheral T cells

Nishiyama, Susumu; Manabe, Noriko; Kubota, Yoshihiro; Ohnìshì, H.; Kitanaka, Akira; Tokuda, Michiaki; Taminato, Tomohiko; Ishida, Toshihiko; Takahara, Jiro; Tanaka, Terukazu

doi:10.1016/j.intimp.2004.11.018

Cited by 24 publications

(16 citation statements)

References 32 publications

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“…Similarly, CsA prevents NF-kB nuclear translocation in stimulated T cells (McCaffrey et al, 1994) by preventing the inducible degradation of IkBa and IkBb; however, in these cells, CsA does not inhibit the processing of p105 to p50 (Marienfeld et al, 1997). CsA is able to block the activation of IL-2 and IL-8 gene expression by NF-kB in T cells (Wechsler et al, 1994;Nishiyama et al, 2005). Like aspirin, CsA has also been shown to be neuroprotective (Meyer et al, 1997).…”

Section: Immunosuppressive Agentsmentioning

confidence: 99%

Inhibitors of NF-κB signaling: 785 and counting

2006

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Section: Immunosuppressive Agentsmentioning

confidence: 99%

Inhibitors of NF-κB signaling: 785 and counting

2006

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“…Interestingly, the nuclear translocation of NF-κB p65 was also inhibited by CsA. This result can be understood on the basis that one of the inhibitory mechanisms of CsA is to interfere with I-κB degradation and to decrease the transcriptional activity of classical NF-κB signaling [26][27][28].…”

Section: Discussionmentioning

confidence: 92%

Suppression of interleukin-2 gene expression by isoeugenol is mediated through down-regulation of NF-AT and NF-κB

Park

Lee

Choi

et al. 2007

International Immunopharmacology

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“…Nishiyama et al reported that the presence of cyclosporine could prevent NF-κB from migrating into the nucleus and instead retains it in the cytoplasm. 30) They proposed that in the early phase of NF-κB activation, cyclosporine may inhibit NF-κB/RelA from translocating to the nucleus and binding to its target sequence in the IL-2 gene promoter region that are involved in human peripheral T cell proliferation. As one of the Ca 2+ sensitive transcription factors, NF-κB is associated with the expression of cytokine, and is involved in the regulation of immune response to infections.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine Nanomicelle Eye Drop: A Novel Medication for Corneal Graft Transplantation Treatment

Zhang

Wang

Zhang

2015

Biological & Pharmaceutical Bulletin

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Corneal transplantation has been used to treat severe eye disease for decades, but the therapeutic effect of the operation is highly compromised by immunological allograft rejection. To improve the success rate of corneal transplantation, we studied the protective effects of cyclosporine nanomicelle eye drops (CNED) on immune rejection after high-risk corneal transplantation and its underlying mechanisms. The therapeutic effects against immune rejection of both conventional cyclosporine eye drop (CCED) and CNED in different concentrations were assessed and compared using animal models of corneal transplantation. In addition, the expression of nuclear factor-κ-gene binding (NF-κB) as well as its target intracellular adhesion molecule 1 (ICAM-1) in the corneal samples obtained from recipients treated with either CCED or CNED was also screened. The results showed that the CNED displayed significantly better effects at suppressing the immune response induced by corneal transplantation compared to CCED. CNED also significantly down-regulated the NF-κB and ICAM-1 expressions, indicating NF-κB might play an important role in the initiation of an immune response against the allograft. Our study demonstrates CNED may suppress the NF-κB pathway to attenuate the immune response, which highlights the possible therapeutic applications of cyclosporine nanomicelle eye drops in corneal transplantation. Key words cyclosporine; nuclear factor-κ-gene binding (NF-κB); corneal allograft transplantation; intracellular adhesion molecule 1 (ICAM-1)Corneal transplantation is the most successful form of solid tissue grafting that serves as a crucial therapy in treating blindness clinically.1) Immunological allograft rejection is considered to be the leading cause of corneal graft failure. Though the 5-year survival rate of low-risk keratoplasty is approximately 90%, the survival rate of high-risk keratoplasty remains below 50% due to immune-mediated rejection even with maximal local immune suppression.2) The high-risk allograft host is characterized by vascularized and inflamed recipient beds, and the pre-existing corneal blood and lymphatic vessels in recipient beds were identified as the primary risk factors for immunological allograft rejection.3) Blood vessels circulates nutrients, oxygen and cells in blood vasculature while lymphatic vessels deliver antigenic materials and donor-derived antigen-presenting cells to the lymph nodes, subsequently inducing immune response against the corneal transplant. 4)Pharmacotherapy for corneal allograft rejection has considerably reduced the rate of graft failure. However, the therapeutic strategy based on corticosteroids remains unimproved over the past decades.5) Multiple side effects of corticosteroids have been observed including cataracts, glaucoma and opportunistic infections, and the EC 50 of the drug varies in either the prevention or the treatment of allograft rejection. 6) Considering the high failure rate of transplantation and the low efficiency of current treatment strategy, the devel...

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Cyclosporin A inhibits the early phase of NF-κB/RelA activation induced by CD28 costimulatory signaling to reduce the IL-2 expression in human peripheral T cells

Cited by 24 publications

References 32 publications

Inhibitors of NF-κB signaling: 785 and counting

Inhibitors of NF-κB signaling: 785 and counting

Suppression of interleukin-2 gene expression by isoeugenol is mediated through down-regulation of NF-AT and NF-κB

Cyclosporine Nanomicelle Eye Drop: A Novel Medication for Corneal Graft Transplantation Treatment

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