Related Experiment Video
Updated: Oct 10, 2025
Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
GRIM19 downregulation-induced pyroptosis of macrophages through NLRP3 pathway in adenomyosis
Haoran Liu1, Yue Zhao1, Yang Yang1
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
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.
Insights
Reduced GRIM19 expression in adenomyosis promotes macrophage pyroptosis and IL-1β release. This inflammatory process drives adenomyosis progression by affecting endometrial stromal cells.
Area of Science:
- Cellular Biology
- Immunology
- Gynecological Pathology
Background:
- Adenomyosis is a gynecological disorder characterized by endometrial tissue growth within the myometrium.
- Pyroptosis, a pro-inflammatory form of programmed cell death, and its role in adenomyosis remain incompletely understood.
- The protein GRIM19 (Gene Regulation: Interferon and Microphthalmia-associated Transcription Factor 19) has been implicated in cellular stress responses.
Purpose of the Study:
- To investigate the role of GRIM19 in macrophage pyroptosis.
- To determine if IL-1β released by pyroptotic macrophages contributes to adenomyosis progression.
- To explore the impact of GRIM19 deficiency on human endometrial stromal cells (HESC).
Main Methods:
- Western blot and RT-PCR were used to analyze GRIM19 expression in endometrial tissues from patients with and without adenomyosis.
- GRIM19 expression was downregulated in THP-1 derived macrophages to assess pyroptosis-related factor expression.
- HESC were co-cultured with GRIM19-depleted macrophages, with and without an IL-1β neutralizing antibody, to evaluate effects on HESC apoptosis, proliferation, and migration.
Main Results:
- GRIM19 expression was significantly lower in adenomyosis tissues.
- Downregulation of GRIM19 in macrophages increased the expression of pyroptosis markers (NLRP3, ASC, caspase-1, GSDMD) and IL-1β release.
- GRIM19 knockdown macrophages inhibited HESC apoptosis and promoted HESC proliferation and migration, effects reversed by IL-1β neutralization.
Conclusions:
- GRIM19 downregulation induces macrophage pyroptosis via the NLRP3 inflammasome pathway.
- Increased IL-1β secretion resulting from GRIM19 deficiency in macrophages promotes adenomyosis progression.
- Targeting GRIM19 or IL-1β may offer therapeutic strategies for adenomyosis.
