High mobility group box-1 promotes inflammation in endometriotic stromal cells through Toll-like receptor 4/nuclear factor-kappa B.
Am J Transl Res
; 13(3): 1400-1410, 2021.
Article
in En
| MEDLINE
| ID: mdl-33841665
ABSTRACT
OBJECTIVE:
To investigate whether high-mobility group box-1 induces cell proliferation, invasion and mediates inflammation in ectopic human endometrial stromal cells through Toll-like receptor 4.METHODS:
Ectopic endometrial specimens were retrieved from patients with ovarian endometrioma having laparoscopy. Ectopic HESCs were treated with H2O2 and recombinant HMGB-1 to induce oxidative stress. The effect of oxidative stress on cell proliferation and invasion was demonstrated. Receptors for HMGB-1 in NF-κB pathway (TLR4, RAGE), angiogenic molecule (VEGF), adhesion molecules (ICAM-1, E-cadherin), and inflammatory cytokines were measured simultaneously to the oxidative stress.RESULTS:
Ectopic HESCs showed markedly decreased cell viability with the increased release of HMGB-1 following treatment with H2O2. When ectopic HESCs were stressed by rHMGB-1, cell proliferation and cell migration numbers increased significantly in a dose-dependent manner. Increased TLR4 and RAGE mRNA and protein expression levels were noted to rHMGB-1 treatment in a dose-dependent manner. VEGF synthesis was also increased by rHMGB-1 treatment. The gene expression of ICAM-1 was upregulated, whereas that of E-cadherin was downregulated with rHMGB-1 treatment. Interleukin-6, IL-1ß, tumor necrosis factor-alpha, and IL-10 were increased significantly by rHMGB-1 treatment. Inversely, after transfection of small interfering RNA against TLR4, rHMGB treatment resulted in decreased cell proliferation and invasion.CONCLUSION:
HMGB-1 activates the NF-κB pathway via TLR4 to increase cell proliferation, invasion, and the production of various inflammatory markers in HESCs. Thus, HMGB-1, TLR4, and NF-κB may represent potential therapeutic targets for the treatment of endometriosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Am J Transl Res
Year:
2021
Document type:
Article