Abstract
Research question
Does the absence of GRIM19 affect pyroptosis of macrophages? Is the release of IL-1β
caused by pyroptosis a relevant factor in the regulation of adenomyosis progression?
Design
Endometrial tissues were collected from patients with (n = 12) and without (n = 12) adenomyosis. GRIM19 expression of adenomyosis tissues was analysed by western
blot and real-time polymerase chain reaction (RT-PCR). In GRIM19 knockdown macrophages,
pyroptosis-related factors expressions were also measured by western blot and RT-PCR.
The human endometrial stromal cells (HESC) were co-cultured with GRIM19-depleted macrophages
and IL-1β neutralizing antibody to detect the effects of pyroptosis of macrophages
on apoptosis, proliferation and migration of HESC.
Results
The expression of GRIM19 was significantly lower in adenomyosis (P = 0.0002). In THP-1-derived macrophages, the expression of NLRP3 (P < 0.0001), ASC (P = 0.0176), caspase-1 (P = 0.0368), GSDMD (P = 0.0453) and IL-1β (P = 0.0208) are increased after downregulation of GRIM19. GRIM19 knockdown induced
the release of IL-1β (P = 0.0195) in THP-1-derived macrophages. The apoptosis of HESC co-cultured with GRIM19
knockdown macrophages was significantly inhibited (P < 0.0001), the proliferation (P = 0.0254) and migration (P < 0.0001) were markedly promoted. Existence of IL-1β neutralizing antibody in supernatants
recovered the effects (P < 0.0001) of GRIM19 knockdown macrophages on HESC.
Conclusions
GRIM19 downregulation induces pyroptosis of macrophages through NLRP3 pathway, increases
the secretion of IL-1β and promotes adenomyosis progression.
KEYWORDS
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Biography
Lan Chao is Chief Physician, Professor, obstetrician and gynaecologist and a doctoral tutor. She is a senior reproductive medicine specialist, specializing in semen analysis, the intravenous pulsatile administration of LH-releasing hormone for ovulation induction and ovarian stimulation in polycystic ovary syndrome.
Key message
Low expression of gene associated with retinoid-interferon-induced mortality 19 induces pyroptosis of macrophages through NOD-Like receptor pyrin domain-containing 3 pathway. Furthermore, pyroptosis of macrophages increases the secretion of IL-1β and may promote adenomyosis progression. These findings may help to identify the cause and pathogenesis of adenomyosis.
Article info
Publication history
Published online: October 24, 2021
Accepted:
October 14,
2021
Received in revised form:
September 29,
2021
Received:
July 9,
2021
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
