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Updated: Jul 23, 2025
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Seasonal coronavirus infections trigger NLRP3 inflammasome activation in macrophages but is therapeutically
Yang Li1, Yining Wang1, Yunlong Li1
1Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands.
Abstract:
Seasonal coronaviruses widely circulate in the global population, and severe complications can occur in specific vulnerable populations. Little is known on their pathogenic mechanisms and no approved treatment is available. Here, we present anecdotal evidence that the level of IL-1β, a hallmark of inflammasome activation, appears elevated in a subset of seasonal coronavirus infected patients. We found that cultured human macrophages support the full life cycle of three cultivatable seasonal coronaviruses. Their infections effectively activate NLRP3 inflammasome activation through TLR4 ligation and NF-κB activation. This activation can be attenuated by specific pharmacological inhibitors and clinically used medications including dexamethasone and flufenamic acid. Interestingly, combination of antiviral and anti-inflammatory drugs simultaneously inhibit seasonal coronavirus-triggered inflammatory response and viral replication. Collectively, these findings show that the TLR4/NF-κB/NLRP3 axis drives seasonal coronavirus triggered-inflammatory response, which in turn represents a viable therapeutic target.
Insights
Seasonal coronaviruses trigger inflammation via the TLR4/NF-κB/NLRP3 pathway. Targeting this axis with anti-inflammatory and antiviral drugs may treat infections and reduce replication.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Seasonal coronaviruses are common but lack approved treatments.
- Pathogenic mechanisms, including inflammasome activation, are poorly understood.
- Elevated Interleukin-1 beta (IL-1β) suggests inflammasome involvement in some patients.
Purpose of the Study:
- To investigate the role of the inflammasome pathway in seasonal coronavirus infection.
- To identify potential therapeutic targets for seasonal coronavirus infections.
Main Methods:
- Cultured human macrophages were infected with seasonal coronaviruses.
- NLRP3 inflammasome activation was assessed via Toll-like receptor 4 (TLR4) ligation and Nuclear Factor-kappa B (NF-κB) activation.
- The effects of pharmacological inhibitors, including dexamethasone and flufenamic acid, were evaluated.
- Combined antiviral and anti-inflammatory drug treatments were tested.
Main Results:
- Human macrophages support the complete lifecycle of seasonal coronaviruses.
- Infection activated the NLRP3 inflammasome through TLR4 and NF-κB pathways.
- Dexamethasone and flufenamic acid attenuated inflammasome activation.
- Combined therapies inhibited both viral replication and the inflammatory response.
Conclusions:
- The TLR4/NF-κB/NLRP3 signaling axis is crucial in seasonal coronavirus-induced inflammation.
- This pathway represents a promising therapeutic target.
- Combination therapy with antiviral and anti-inflammatory drugs shows potential for treating seasonal coronaviruses.
