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(5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells
- Source :
-
International Immunopharmacology . Jan2009, Vol. 9 Issue 1, p63-69. 7p. - Publication Year :
- 2009
-
Abstract
- Abstract: Aim: (5R)-5-hydroxytriptolide (LLDT-8) displayed immunosuppressive activities both in vitro and in autoimmune disease models. Here, we aim to further clarify the effect of LLDT-8 on the immune responses of human peripheral blood mononuclear cells (PBMC). Method: Cell proliferation of human PBMC from healthy donors was evaluated by [3H]-thymidine uptake. NK cell cytotoxicity was assayed using K562 cells in a [3H] lysis assay. Cytokine production was determined by enzyme-linked immunosorbent assay. The expression of cell surface molecules was detected with flow cytometry. The mRNA expression and the protein phosphorylation levels were detected by RT-PCR and Western immunoblot assay. Results: LLDT-8 at 25 and 50 nM significantly inhibited the PHA- and recall antigens-induced T cell proliferation, and suppressed mixed lymphocyte reaction. LLDT-8 reduced cytokines production (IFN-γ, IL-2, TNF-α) in PHA- and Sac-activated PBMC. LLDT-8 did not alter the increased expression of MHC class I/II and B7.1, but reduced B7.2 by approximately 30%. No effect of LLDT-8 was observed for the expression of T cell activation markers (CD69, CD154). However, LLDT-8 significantly reduced IFN-γ-expressing T cell percentages and IFN-γ mRNA transcription in PHA-activated T cells. It also inhibited the phosphorylation levels of JNK and p38. LLDT-8 did not affect NK cytotoxic activity against K562 cells. Conclusion: LLDT-8 was a promising immunosuppressant for human immune-related diseases. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 9
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 36016662
- Full Text :
- https://doi.org/10.1016/j.intimp.2008.09.014