Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 04, 2024 1 month, 2 weeks, 4 days, 15 hours, 44 minutes ago
Medical News: Researchers from the University of Ferrara in Italy have made significant strides in understanding how interactions between Toll-like Receptor 4 (TLR4) and SARS-CoV-2 may drive severe inflammatory responses in COVID-19 patients. By focusing on the role of microRNAs - small, non-coding RNA molecules involved in gene regulation - scientists believe they may have found a way to mitigate the harmful effects of this interaction and possibly lessen the severity of COVID-19 symptoms. This
Medical News report dives into their hypothesis and the implications for developing targeted therapies that could reduce inflammation by influencing TLR4 activity.
TLR4 and COVID-19, Uncovering the Role of MicroRNAs in Reducing Inflammation
TLR4: The Inflammatory Gateway
TLR4 is a receptor known for its role in recognizing pathogens and triggering immune responses. During SARS-CoV-2 infections, this receptor is activated, leading to an inflammatory response. In severe cases, this inflammation becomes excessive, contributing to complications like the "cytokine storm," where the immune system releases too many signaling molecules, often resulting in tissue damage.
The University of Ferrara’s researchers believe that controlling TLR4 activation could be a potential therapeutic strategy to prevent such outcomes. Their findings suggest that microRNAs - specifically miR-93 and miR-145 - can regulate TLR4 activity. By influencing the inflammatory pathway through these microRNAs, it may be possible to reduce the body's overactive immune response.
MicroRNAs: Tiny Molecules with Big Impact
MicroRNAs are small molecules that don’t code for proteins but play a major role in regulating genes. In this study, miR-93 and miR-145 emerged as key players in modulating the immune response. Specifically, they interact with the TLR4 signaling pathway, impacting the production of various pro-inflammatory proteins.
This hypothesis highlights the potential of using synthetic microRNAs, or "ago-miRNAs," to mimic the effects of miR-93 and miR-145. When introduced into target cells, these synthetic molecules can inhibit TLR4, reducing the production of pro-inflammatory proteins. This targeted approach represents a promising avenue for reducing inflammation without broadly suppressing the immune system.
Reducing the Cytokine Storm with MicroRNA Therapy
One of the most dangerous outcomes of severe COVID-19 infections is the cytokine storm, an intense inflammatory response that can lead to organ damage. The study demonstrates that microRNA therapy could potentially prevent this. By inhibiting TLR4, miR-93 and miR-145 reduce the activation of NF-kB, a protein complex responsible for regulating the genes involved in inflammation. With reduced NF-kB activity, the production of inflammatory proteins like interleukin-8 (IL-8) decreases, limiting the cytokine storm’s impact.
The Mechanics of TLR4 and NF-kB Interaction
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In normal conditions, TLR4 activation is controlled to prevent excessive inflammation. However, during SARS-CoV-2 infection, the spike protein of the virus binds to TLR4, activating NF-kB. This process involves a complex interaction where TLR4 signals to release NF-kB into the nucleus of cells, where it turns on genes responsible for inflammation. MicroRNAs like miR-93 can interrupt this pathway by binding to TLR4 and preventing it from activating NF-kB.
The researchers claim that blocking this pathway could protect cells from excessive inflammatory responses. When miR-93 and miR-145 are introduced, they essentially silence TLR4, blocking the entire pathway and preventing the body from entering an inflammatory overdrive.
Potential for New COVID-19 Treatments
The insights gained from this hypothesis suggest that microRNA therapy could be used as an adjunct treatment for COVID-19. The idea is that synthetic microRNAs could be administered to high-risk patients, particularly those at risk of severe inflammatory responses. By preemptively calming the immune system's overreaction, these treatments could reduce hospitalizations and improve outcomes for patients with severe COVID-19.
The application of microRNA therapy is still in its experimental phase. However, its potential is evident. As researchers continue to explore this approach, it could pave the way for treatments that are not only effective against COVID-19 but also applicable to other diseases characterized by excessive inflammation.
Conclusion
The discovery that microRNAs like miR-93 and miR-145 can regulate TLR4 provides a promising new avenue for treating severe COVID-19. By targeting the TLR4/NF-kB pathway, these small RNA molecules could reduce the inflammatory responses associated with the disease. This approach offers a more targeted, nuanced way to manage COVID-19's severe symptoms without compromising the immune system's essential functions.
With further research, microRNA therapy could become a valuable tool in the fight against COVID-19 and potentially other inflammatory diseases. By targeting specific aspects of the immune response, these therapies may offer a safer, more effective way to manage inflammation and improve patient outcomes.
The hypothesis was published as a letter in the in the peer-reviewed Journal of Inflammation Research.
https://www.dovepress.com/interplay-of-tlr4-and-sars-cov-2-possible-involvement-of-micrornas-let-peer-reviewed-fulltext-article-JIR
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https://www.thailandmedical.news/news/ginsenoside-rh2-from-red-ginseng-reduces-inflammation-by-blocking-tlr4-dimerization-and-key-immune-pathways
https://www.thailandmedical.news/news/tlr2-and-tlr4-are-novel-activating-receptors-for-sars-cov-2-spike-protein-in-nk-cells
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