Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory Response via the lncRNA-SNHG1/HMGB1 Axis in Lipopolysaccharide-Induced Acute Lung Injury

Abstract

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

Cryotherapy Attenuates Inflammation via the lncRNA SNHG1/miR-9-5p/NFKB1 Regulatory Axis in Periodontal Ligament Cells

“…It has been reported that SNHG1 participates in a variety of LPSinduced inflammation and promotes the production of proinflammatory cytokines [19,20]. Interestingly, SNHG1 is a direct transcriptional target of NFKB subunit p65 that promotes the expression of proinflammatory cytokines in acute lung injury (ALI) [21]. SNHG1 may form a positive feedback loop with the NF-κB pathway.…”

“…Interestingly, we found that the lncRNA SNHG1 mediated crosstalk with NFKB1 via two miRNAs, including miR-9-5p and miR-340-5p (Figure 6B). lncRNA SNHG1 has previously been reported to be significantly associated with inflammatory gene expression and promote LPS-induced inflammatory responses [19][20][21]. Thus, we speculated that SNHG1-miR-9-5p/miR-340-5p-NFKB1 axis might play an important role in the reduction in inflammation by cryotherapy by regulating NFKB1 expression.…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Similarly, limiting RAGE-mediated inflammation may be beneficial in ARDS treatment. It is reported that Dexmedetomidine [ 234 ], Calycosin [ 235 ], and Tanreqing [ 236 ] alleviate inflammation mediated by RAGE and TLR4 receptors via inhibiting HMGB1 signaling. Notably, a clinical trial of Dexmedetomidine for ARDS in critical care COVID-19 patients is under investigation (NCT04358627).…”

Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases

“…In cholangiocarcinoma cell lines, SNHG1 is associated with increased proliferation and invasion, mediated by NF-κB activation through the miR-140/TLR4 axis, contributing to an inflammatory TME [ 171 ]. In an LPS-induced acute lung injury model, SNHG1 is upregulated in M1 polarized THP-1 cells, enhancing NF-κB activation and inflammation through interaction with HMGB1 [ 114 ]. However, SNHG1’s specific role in macrophage-related TME remains unexplored.…”