Back to Search
Start Over
Atractylenolide I modulates ovarian cancer cell-mediated immunosuppression by blocking MD-2/TLR4 complex-mediated MyD88/NF-κB signaling in vitro.
- Source :
- Journal of Translational Medicine; 4/27/2016, Vol. 14, p1-12, 12p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>TLR4/MD-2 complex-mediated MyD88-dependent activation of NF-κB and Akt promotes tumor-associated immunosuppression in epithelial ovarian cancer (EOC) via induction of immunesuppressive cytokines and indoleamine 2,3-dioxygenase (IDO). Atractylenolide I (AO-1) is a naturally occurring sesquiterpene lactone known to change the conformational ensemble of human MD-2 on EOC cells. This study examined the modulation by AO-1 of TLR4/MD-2 complex-mediated MyD88/NF-κB signaling.<bold>Methods: </bold>The expression and activation of NF-κB, Akt and IDO1 by MyD88(+) EOC SKOV3 cells was determined using western blot; the TLR4/MD-2 complex on SKOV3 cells and the phenotype of T lymphocytes were determined using flow cytometry; IDO activity was evaluated by measuring L-kynurenine; Immunesuppressive cytokines were detected using ELISA; T-cell proliferation to mitogen stimulation was assessed by MTT assay; the cytotoxicity of lymphocytes and NK cells was measured using LDH-cytotoxicity assay.<bold>Results: </bold>AO-1 could down-regulate expression of TLR4/MD-2 complex, resulting in downregulation of MyD88/NF-κB signaling and activation of NF-κB, Akt and IDO1 and secretion of IL-6, TGF-β1, VEGF and IL-17A by EOC SKOV3 cells, and further reduce increased levels of regulatory T cells (Treg cells) and improve decreased proliferative response and antitumor cytotoxicity of T lymphocytes exposed to EOC SKOV3 cell supernatant.<bold>Conclusion: </bold>AO-1 may reverse EOC cell-mediated immunosuppression through blocking TLR4/MD-2 complex-mediated MyD88/NF-κB signaling. [ABSTRACT FROM AUTHOR]
- Subjects :
- ATRACTYLODES
OVARIAN epithelial cancer
CANCER cells
IMMUNOSUPPRESSION
CYTOKINES
AMINO acids
BIOCHEMISTRY
CARRIER proteins
CELL lines
CELL physiology
CELL receptors
CELLULAR signal transduction
HYDROCARBONS
IMMUNITY
PHENOMENOLOGY
ORGANIC compounds
OVARIAN tumors
OXIDOREDUCTASES
T cells
TRANSFERASES
DNA-binding proteins
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 115062419
- Full Text :
- https://doi.org/10.1186/s12967-016-0845-5