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KMID : 0043320230460110897
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Archives of Pharmacal Research
2023 Volume.46 No. 11 p.897 ~ p.906
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Human milk oligosaccharides 3￠-sialyllactose and 6￠-sialyllactose attenuate LPS-induced lung injury by inhibiting STAT1 and NF-kB signaling pathways
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Jin Yu-Jin
Jeon Hye-Su
Thuy Le Lam Nguyen
Kim Li-La
Heo Kyung-Sun
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Abstract
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Acute lung injury (ALI) is the leading cause of respiratory diseases induced by uncontrolled infl ammation and cell death.
Lipopolysaccharide (LPS) is a major trigger of ALI in the progression through macrophage diff erentiation and the acceleratedrelease of pro-infl ammatory cytokines. The present study aimed to investigate the protective eff ects of human milkoligosaccharides, specifi cally 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL), on LPS-induced ALI and elucidate theirunderlying signaling pathways. The inhibitory eff ects of 3′-SL and 6′-SL on infl ammation were evaluated using LPS-treatedRAW 264.7 macrophages. To establish the ALI model, mice were treated with 10 mg/kg LPS for 24 h. Histological changesin the lung tissues were assessed using hematoxylin and eosin staining and immunofl uorescence. LPS causes thickeningof the alveolar wall infi ltration of immune cells in lung tissues and increased serum levels of TNF-α, IL-1β, and GM-CSF.
However, these eff ects were signifi cantly alleviated by 100 mg/kg of 3′-SL and 6′-SL. Consistent with the inhibitory eff ectsof 3′-SL and 6′-SL on LPS-induced pro-infl ammatory cytokine secretion in serum, 3′-SL and 6′-SL suppressed mRNAexpression of TNF-α, IL-1β, MCP-1, iNOS, and COX2 in LPS-induced RAW 264.7 cells. Mechanistically, 3′-SL and 6′-SLabolished LPS-mediated phosphorylation of NF-κB and STAT1. Interestingly, fl udarabine treatment, a STAT1 inhibitor, didnot aff ect LPS-mediated NF-κB phosphorylation. In summary, 3′-SL and 6′-SL protect LPS-induced macrophage activationand ALI through the STAT1 and NF-κB signaling pathways.
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KEYWORD
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Inflammation, Lung injury, Sialyllactoses, Lipopolysaccharide
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