RETRACTED: Notoginsenoside R1 protects human keratinocytes HaCaT from LPS-induced inflammatory injury by downregulation of Myd88

Abstract

Burn injury is a gigantic challenge in public health which brings multiple negative effects to patients both in physical and spiritual aspects. Inflammation plays vital roles in the progression of burn injury, and our study investigated whether notoginsenoside R1 (NGR1) alleviated lipopolysaccharide (LPS)-induced human keratinocyte HaCaT cell inflammatory injury. Inflammatory injury was induced by LPS in HaCaT cells. Stimulated cells were then treated by NGR1 in different concentrations. Cell viability and cell apoptosis were detected by Cell Counting Kit-8 and flow cytometry, respectively. The concentration of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The accumulated levels of apoptosis-related proteins (caspase-3 and caspase-9), nuclear factor κB (NF-κB), p38 mitogen-activated protein kinase (p38MAPK) signal pathways–related proteins (p65, IκBα, and p38MAPK), and myeloid differentiation primary response 88 (MyD88) were examined by western blot. Transfection was used to alter the expression of MyD88. We found that LPS stimulated HaCaT cells and induced cell inflammation, evidenced by decreasing cell viability, increasing cell apoptosis, and elevating TNF-α and IL-6 expressions. Then, we found that NGR1 reversed the results by enhancing cell viability, inhibiting cell apoptosis, and reducing TNF-α and IL-6 expressions. In addition, NGR1 decreased the phosphorylation of p65, IκBα, and p38MAPK, which increased by LPS. Moreover, NGR1 negatively regulated the expression of MyD88, and transfection with pMyD88 led to the opposite results with what showed by NGR1 in LPS-stimulated HaCaT cells. To sum up, NGR1 alleviates LPS-induced HaCaT cell inflammatory injury by downregulation of MyD88, as well as inactivation of NF-κB and p38MAPK signal pathways.

MyD88 Regulates LPS-induced NF-ĸB/MAPK Cytokines and Promotes Inflammation and Malignancy in Colorectal Cancer Cells

“…Silencing of MyD88 in SW480 and HCT116 cells inhibited the increased migration, invasion and proliferation after treatment with LPS. These studies indicated that LPS-MyD88 signaling-induced inflammation may participate in the progression of human colorectal cancer cells, consistent with Zhang et al (26), who had reported that knockdown of MyD88 can reduce LPS-induced expression of inflammatory factors (26). We further demonstrated the role of MyD88 in LPS-promoted expression of inflammatory cytokines and migration, invasion, and proliferation in colorectal cancer cells.…”

“…How LPS-induced pathways react is not fully understood. Previous studies have reported that NF-ĸB/MAPK is very important in the MyD88 signaling pathway induced by LPS (26)(27)(28). The NF-ĸB/MAPK signaling pathway plays important roles in inflammatory responses.…”

Labdane-Type Diterpenes from the Aerial Parts of Rydingia persica: Their Absolute Configurations and Protective Effects on LPS-Induced Inflammation in Keratinocytes

“…Consequently, alleviation of inflammatory injury is a pivotal step in the prevention of skin/tissue injury progression. 3 The inflammatory phase intersects remarkably with primary hemostasis, occurring during the first 72 h after tissue/skin injury. 4 This stage is associated with a complex series of molecular signals and eventually facilitates neutrophil and monocyte infiltration to the wound area, resulting in restraint of further tissue damage and elimination of pathogenic organisms and external remnants.…”

<p>Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases</p>

“…92 Burn injury shows dramatically negative effects on patients by triggering inflammation at least. NG-R1 has been demonstrated to counteract inflammatory injury in LPS-treated human keratinocyte HaCaT cells, as indicated by downregulation of MyD88 expression, inactivation of p38 MAPK and NF-κB signaling pathways, and suppression of cell apoptosis 93 (Table 1).…”