TY - JOUR
T1 - Alpha-lipoic acid plays a role in endometriosis
T2 - New evidence on inflammasome-mediated interleukin production, cellular adhesion and invasion
AU - Di Nicuolo, Fiorella
AU - Castellani, Roberta
AU - Nardone, Alessandra De Cicco
AU - Barbaro, Greta
AU - Paciullo, Carmela
AU - Pontecorvi, Alfredo
AU - Scambia, Giovanni
AU - Di Simone, Nicoletta
N1 - Funding Information:
Funding: The study was supported by a research grant from the Università Cattolica del Sacro Cuore, Roma (D1, 2017) and by Laborest Italia srl.
Funding Information:
The study was supported by a research grant from the Universit? Cattolica del Sacro Cuore, Roma (D1, 2017) and by Laborest Italia srl.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/2
Y1 - 2021/1/2
N2 - Endometriosis is an estrogen-linked gynecological disease defined by the presence of endometrial tissue on extrauterine sites where it forms invasive lesions. Alterations in estrogen-mediated cellular signaling seems to have an essential role in the pathogenesis of endometriosis. Higher estrogen receptor (ER)-β levels and enhanced ER-β activity were detected in endometriotic tissues. It is well known that ER-β interacts with components of the cytoplasmic inflammasome-3 (NALP-3), the NALP-3 activation increases interleukin (IL)-1β and IL-18, enhancing cellular adhesion and proliferation. Otherwise, the inhibition of ER-β activity suppresses the ectopic lesions growth. The present study aims to investigate the potential effect of α-lipoic acid (ALA) on NALP-3 and ER-β expression using a western blot analysis, NALP-3-induced cytokines production by ELISA, migration and invasion of immortalized epithelial (12Z) and stromal endometriotic cells (22B) using a 3D culture invasion assay, and matrix-metalloprotease (MMPs) activity using gelatin zymography. ALA significantly reduces ER-β, NALP-3 protein expression/activity and the secretion of IL-1β and IL-18 in both 12Z and 22B cells. ALA treatment reduces cellular adhesion and invasion via a lower expression of adhesion molecules and MMPs activities. These results provide convincing evidence that ALA might inhibit endometriosis progression.
AB - Endometriosis is an estrogen-linked gynecological disease defined by the presence of endometrial tissue on extrauterine sites where it forms invasive lesions. Alterations in estrogen-mediated cellular signaling seems to have an essential role in the pathogenesis of endometriosis. Higher estrogen receptor (ER)-β levels and enhanced ER-β activity were detected in endometriotic tissues. It is well known that ER-β interacts with components of the cytoplasmic inflammasome-3 (NALP-3), the NALP-3 activation increases interleukin (IL)-1β and IL-18, enhancing cellular adhesion and proliferation. Otherwise, the inhibition of ER-β activity suppresses the ectopic lesions growth. The present study aims to investigate the potential effect of α-lipoic acid (ALA) on NALP-3 and ER-β expression using a western blot analysis, NALP-3-induced cytokines production by ELISA, migration and invasion of immortalized epithelial (12Z) and stromal endometriotic cells (22B) using a 3D culture invasion assay, and matrix-metalloprotease (MMPs) activity using gelatin zymography. ALA significantly reduces ER-β, NALP-3 protein expression/activity and the secretion of IL-1β and IL-18 in both 12Z and 22B cells. ALA treatment reduces cellular adhesion and invasion via a lower expression of adhesion molecules and MMPs activities. These results provide convincing evidence that ALA might inhibit endometriosis progression.
KW - Endometriosis
KW - Estrogen receptor (ER)
KW - Lipoic acid
KW - NALP-3 inflammasome
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U2 - 10.3390/molecules26020288
DO - 10.3390/molecules26020288
M3 - Article
C2 - 33430114
AN - SCOPUS:85099889641
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 2
M1 - 288
ER -