FK506, a promising new immunosuppressant, is currently under clinical investigation. Because dose-dependent toxicity is possible, blood concentrations of FK506 should be monitored. We improved the original ELISA of FK506 by shortening the incubation time. With some modification of materials, results are obtained within 6 h instead of 2 days, with similar or even better precision. Internal and e...

To elucidate the effect of FK506 on Ca2+ oscillations in airway epithelium, we investigated cultured cow tracheal epithelial cells with a Ca2+ image-analysis system. ATP (1 μM) induced long-lasting Ca2+ oscillations, having nearly constant peak values (300-400 nM) and intervals (20-40 s) in subconfluent cells but not in confluent cells. These responses were gradually attenuated and abolished by...

Epstein-Barr virus (EBV)-driven posttransplantation lymphoproliferative disease (PTLD) is a serious complication of immunosuppression after either stem cell transplantation (SCT) or solid organ transplantation (SOT). Adoptive transfer of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) is an effective prophylaxis and treatment for PTLD after SCT, but not for PTLD after SOT when pharmacologic imm...

BACKGROUND AND PURPOSE Previous studies have demonstrated that the immunosuppressant FK506 provides neuroprotection in experimental brain injury and suggest that this action may be mediated by suppression of neuronal nitric oxide synthase activation that occurs after ischemic depolarization. We sought to determine whether FK506 reduces histological injury after middle cerebral artery occlusion ...

FK506 binding proteins (FKBPs 12 and 12.6) interact with ryanodine receptor (RyR) and modulate its functions. FK506 binds to and reverses effects of FKBP on RyR, thus increasing RyR sensitivity to Ca , decreasing RyR cooperativity, and increasing RyR open probability. FK506 would thus be expected to have an effect on excitation-contraction coupling, but which of these FK506 effects predominates...

A FK506 analogue containing a non-natural starter unit was obtained through mutasynthesis by feeding cultures of Streptomyces sp. KCTC 11604BP fkbO deletion mutant with 3-cyclohexene-1-carboxylic acid. The structure of the new compound, 32-dehydroxy-FK506, and its biological activities were determined.

FK506 (also known as tacrolimus) is a potent immunosuppressive agent that is widely used in the treatment of graft-rejection and autoimmune diseases. FK506 has attracted additional attention owing to its potential role in osteogenic differentiation and bone formation. MicroRNAs (miRNAs) have been demonstrated to serve important roles in the regulation of osteogenic differentiation; however, ide...

Cyclosporine A (CsA) and FK506 suppress T cell activation by inhibiting calcineurin and the calcineurin-dependent transcription factors nuclear factor of activated T cells (NFATc), which are central regulators of T cell function. It was reported that CsA up-regulated the transcription of transforming growth factor1 (TGF1) in lymphocytes and other cells and activated its promoter in A549 lung ca...

PURPOSE To investigate the efficacy and mechanism of tacrolimus(FK506), which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) expression in a murine keratitis model induced by Aspergillus fumigatus. METHOD TREM-1 was detected in 11 fungus-infected human corneas by quantitative real-time PCR (qRT-PCR). RAW264.7 macrophages were di...

The mitochondrial toxin 3-nitropropionic acid (3-NP) has been largely used to study neurodegenerative disorders in which bioenergetic defects are implicated. In the present study, we analyzed the molecular pathways involved in FK506 neuroprotection against cell death induced by 3-NP, using cultured cortical neurons. 3-NP induced cytochrome c release and increased caspases -2, -3, -8, and -9-lik...