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Updated: Oct 30, 2025
Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
Luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation
Yongpeng Zou1, Xing Luo1, Yi Feng2
1Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China.
Abstract:
Pyroptosis plays an important role in the pathogenesis of numerous infectious, autoimmune, and inflammatory diseases, which makes it a promising target for intervention. In this study, the effect of luteolin on pyroptosis and the underlying mechanism were investigated using the canonical NLRP3 inflammasome in THP-1 macrophages induced by LPS/ATP. The results showed that luteolin exhibited a potent preventive effect on THP-1 macrophage pyroptosis, as evidenced by the increase in cell viability and the decrease in LDH release. Moreover, luteolin was found to significantly reduce the expression of NLRP3, pro-CASP-1 and CASP-1, which are the key components of NLRP3 inflammasome, as well as the expression of N-GSDMD and IL-1β, and we proved that the inhibition of luteolin on NLRP3 inflammasome activation is ROS-dependent. Furthermore, it was demonstrated that luteolin promoted Nrf2 nuclear translocation, thereby increasing the expression of HO-1 that reduces ROS production, while the anti-pyroptotic effect of luteolin was reversed by a specific Nrf2 inhibitor. Additionally, luteolin inhibited NF-κB p65 phosphorylation and nuclear translocation. In summary, we conclude that luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation as well as NF-κB inactivation. These results support luteolin as a potential bioactive chemical against pyroptosis-related inflammatory diseases.
Insights
Luteolin effectively prevents pyroptosis, a cell death process implicated in inflammatory diseases. This natural compound works by inhibiting the NLRP3 inflammasome pathway, offering potential therapeutic benefits.
Area of Science:
- Cellular Biology
- Immunology
- Pharmacology
Background:
- Pyroptosis is a key mechanism in inflammatory and autoimmune diseases.
- Targeting pyroptosis offers a promising therapeutic strategy.
- The NLRP3 inflammasome is a central regulator of pyroptosis.
Purpose of the Study:
- To investigate the effect of luteolin on pyroptosis in macrophages.
- To elucidate the underlying molecular mechanisms of luteolin's action.
- To assess luteolin's potential as a therapeutic agent for pyroptosis-related conditions.
Main Methods:
- THP-1 macrophages were induced to undergo pyroptosis using LPS/ATP.
- Luteolin's effects on cell viability, LDH release, and key pyroptosis-related proteins (NLRP3, pro-CASP-1, CASP-1, N-GSDMD, IL-1β) were assessed.
- The roles of reactive oxygen species (ROS), Nrf2, and NF-κB pathways were investigated using specific inhibitors and by measuring protein translocation and phosphorylation.
Main Results:
- Luteolin significantly inhibited LPS/ATP-induced pyroptosis in THP-1 macrophages, increasing cell viability and reducing LDH release.
- Luteolin suppressed the expression of NLRP3 inflammasome components and downstream effectors (N-GSDMD, IL-1β).
- Luteolin's anti-pyroptotic effect was mediated by ROS suppression through Nrf2 activation and subsequent HO-1 expression, and by inhibiting NF-κB p65 activation.
Conclusions:
- Luteolin effectively prevents pyroptosis by inhibiting the NLRP3 inflammasome pathway in macrophages.
- The mechanism involves ROS suppression via Nrf2 activation and NF-κB inactivation.
- Luteolin demonstrates potential as a therapeutic compound for diseases associated with pyroptosis.
