6'-Sialylactose abolished lipopolysaccharide-induced inflammation and hyper-permeability in endothelial cells

Area of Science:

• Endothelial biology
• Immunology
• Glycobiology

Background:

• Endothelial dysfunction involves barrier disruption and impaired cell migration.
• Human milk oligosaccharides, like 6'-sialylactose (6'-SL), possess anti-inflammatory properties.
• Lipopolysaccharide (LPS) induces endothelial inflammation and barrier damage.

Purpose of the Study:

• To investigate the protective effects of 6'-SL against LPS-induced endothelial inflammation.
• To elucidate the molecular mechanisms underlying 6'-SL's action on endothelial barrier function.

Main Methods:

• Assessing cell migration and endothelial barrier integrity.
• Analyzing MAPK and NF-κB pathway activation.
• Quantifying expression of junctional proteins (PECAM-1, ZO-1, occludin) and inflammatory cytokines (TNF-α, IL-1β, MCP-1, VCAM-1, ICAM-1).
• Evaluating STAT3 activation and nuclear translocation.
• In vivo studies using mouse aorta models.

Main Results:

• LPS abolished cell migration and activated MAPK and NF-κB pathways.
• 6'-SL suppressed LPS-induced inflammation by inhibiting MAPK pathways (ERK1/2, p38, JNK).
• 6'-SL upregulated PECAM-1 and tight junction proteins (ZO-1, occludin), countering LPS-induced downregulation.
• 6'-SL inhibited NF-κB nuclear translocation and reduced inflammatory cytokines.
• 6'-SL attenuated STAT3 activation, mitigating endothelial hyperpermeability.
• In vivo, 6'-SL reversed LPS-induced VCAM-1 overexpression and ZO-1 disassembly in mouse aortas.

Conclusions:

• 6'-SL demonstrates potent anti-inflammatory effects against LPS-induced endothelial damage.
• 6'-SL preserves endothelial barrier function by modulating MAPK, NF-κB, and STAT3 signaling.
• 6'-SL shows promise as a therapeutic agent for inflammatory conditions and endothelial hyperpermeability.