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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Orally administered BZL-sRNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice
Dandan Zhao1, Yuhao Qin1, Jiaqi Liu1
1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Beijing, 100005, China.
Abstract:
The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.
Insights
BZL-sRNA-20, a herbal small RNA, effectively inhibits Toll-like receptor 4 (TLR4) and reduces inflammation. This compound shows promise as a broad-acting therapeutic for acute respiratory distress syndrome (ARDS) and acute lung injury (ALI).
Area of Science:
- Molecular Biology
- Immunology
- Pharmacology
Background:
- Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are severe complications of infections like COVID-19.
- Toll-like receptor 4 (TLR4) plays a critical role in the inflammatory pathways leading to ARDS and ALI.
- Herbal small RNAs (sRNAs) have emerged as potential therapeutic agents.
Purpose of the Study:
- To investigate the inhibitory effects of BZL-sRNA-20 on TLR4 and pro-inflammatory cytokines.
- To evaluate the efficacy of BZL-sRNA-20 against viral infections and LPS-induced lung injury.
- To explore the potential of BZL-sRNA-20 as a pan-anti-ARDS/ALI drug.
Main Methods:
- BZL-sRNA-20 was assessed for its inhibitory activity against TLR4 and cytokine production induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)).
- Cell viability assays were performed on cells infected with avian influenza H5N1, SARS-CoV-2, and its variants of concern (VOCs).
- A mouse model of acute lung injury induced by LPS and SARS-CoV-2 was used to evaluate the therapeutic effect of BZL-sRNA-20 delivered via a medical decoctosome mimic (bencaosome).
Main Results:
- BZL-sRNA-20 demonstrated potent inhibition of TLR4 and pro-inflammatory cytokines.
- The compound reduced intracellular cytokine levels induced by LTA and poly (I:C).
- BZL-sRNA-20 significantly protected cells against H5N1, SARS-CoV-2, and VOC infections, and ameliorated lung injury in mice.
Conclusions:
- BZL-sRNA-20 effectively targets the TLR4 pathway, reducing inflammation and protecting against lung injury.
- The findings suggest BZL-sRNA-20 has broad-spectrum antiviral and anti-inflammatory properties.
- BZL-sRNA-20 holds potential as a novel therapeutic agent for ARDS and ALI.
