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Mechanism of FK506 Induced TNF Related Apoptosis in Jurkat T Cells.

S. Chung, S. Choi.

Department of Surgery, Chonnam National University Hospital, Gwangju, Korea.

Meeting: 2016 American Transplant Congress

Abstract number: A42

Keywords: Apoptosis, FK506, T cells, Tumor necrosis factor (TNF)

Session Information

Date: Saturday, June 11, 2016

Session Name: Poster Session A: B cells & AMR, Alloreactivity, Immune Regulation & Regulatory T Cells, T Cell Biology and Alloreactivity, Immunesuppression

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Halls C&D

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Purpose: To elucidate the mechanism of FK506 induced TRAIL(TNF related apoptosis inducing ligand) –R1(DR4) and TRAIL-R2(DR5) in FK506-treated Jurkat T cells. And signal transduction pathway of TNF-related events was studied.

Methods: The catalytic activation of caspase-3 and caspase-9 proteases was determined by digestion of fluorogenic biosubstrates and western blot with anti-caspase-3 and anti-caspase-9 antibodies. The levels of mRNA and proteins for p53, Bax, PUMA, proline oxidase, TRAIL(TNF related apoptosis inducing ligand), TRAIL-R1(DR4), TRAIL-R2(DR5), Fas, FasL, TNF-α, IL-6, and NKκB were measured by RT-PCR and western blot with specific antibodies. Also we further examined the localization of TRAIL family proteins using by fluorescent microscope with specific TRAIL family antibodies.

Results: FK506 decreased the viability of Jurkat T cells dose- and time-dependently along with catalytic activation of caspase-3 and caspase-9, p53 phosphorylation, and changes in expression levels of Bax, PUMA, and proline oxidase protein. It caused an increase in expression of TRAIL, TRAIL-R1(DR4), TRAIL-R2(DR5), Fas, and FasL in the levels of mRNA and proteins of Jurkat T cells. Furthermore, FK506 increased extracellular release of TNF-α and IL-6 cytokines in Jurkat T cells. It also induced the transactivation of NKκB through the dephosphrylation of Ser486 residues in Jurkat t cells.

Conclusion: These results suggest that FK506 induces apoptotic death of Jurkat cells through activation of caspase family protease, Bcl-2 family protein-related mitochondrial dysfunction, and activation of death-receptor mediated signaling pathways.

CITATION INFORMATION: Chung S, Choi S. Mechanism of FK506 Induced TNF Related Apoptosis in Jurkat T Cells. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Chung S, Choi S. Mechanism of FK506 Induced TNF Related Apoptosis in Jurkat T Cells. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/mechanism-of-fk506-induced-tnf-related-apoptosis-in-jurkat-t-cells/. Accessed January 19, 2021.

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