Lipopolysaccharide (LPS) is an important pathogenic factor and plays a key role in human diseases such as fever, shock, and sepsis. Blocking the toxicity of LPS through antagonism is considered the best choice for the treatment of LPS-induced diseases. In this research, nucleic acid aptamer LA27, which was previously selected and optimized by our group, was used as an LPS inhibitor to treat human HepG2 cells stimulated by LPS from four different sources (StLPS, EcoliLPS, PaLPS, and SeLPS): the levels of expression of three inflammatory cytokines factors (TNF-α, IL-1β, and IL-6) were evaluated by ELISA on LA27-treated and untreated cells incubated for 12 h with LPS. The results of the assays indicated that LA27 exhibited considerable anti-inflammatory activity. The binding site and interactions between aptamer LA27 and LPSs were also simulated using Molecular Operating Environment (MOE) 2018 software. MOE simulation results showed that, under a combination of the hydrophobic interaction, hydrogen bonding, and electrostatic interactions, the fatty acid chain of LPS could interact with the wide hydrophobic region of the aptamer, constituting its major groove, and formed stable complex of T-type. The present research indicated that LA27 might be a potential therapeutic agent for sepsis and other diseases, which provides a new path for the development of LPS antagonists.
Keywords: Aptamer; Inflammation; Lipopolysaccharide; T-type complex.
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