Hydroxypropyl Methylcellulose as a Functional Dietary Fiber Preserves Intestinal Barrier Integrity via NF-κB...

Area of Science:

• Gastroenterology
• Cell Biology
• Pharmacology

Background:

• Intestinal epithelial barrier integrity is vital for gut homeostasis.
• Pro-inflammatory cytokines disrupt tight junctions (TJs), leading to barrier dysfunction and inflammatory bowel disease.
• Hydroxypropyl methylcellulose (HPMC) is a common excipient and dietary fiber with potential therapeutic properties.

Purpose of the Study:

• To investigate the protective effects of HPMC against cytokine-induced epithelial barrier dysfunction in Caco-2 cell models.
• To determine HPMC's impact on TJ protein expression, inflammatory mediator secretion, and NF-κB signaling.

Main Methods:

• Caco-2 cell monolayers were treated with HPMC and subsequently exposed to pro-inflammatory cytokines (TNF-α, IFN-γ).
• Transepithelial electrical resistance (TEER) and FITC-dextran paracellular permeability were measured.
• Secretion of inflammatory mediators (IL-8, IL-1β, IL-6, MCP-1) was quantified.
• Expression and localization of TJ proteins (zonula occludens-1, occludin) were assessed.
• NF-κB activation was evaluated by monitoring IκBα phosphorylation and nuclear translocation.

Main Results:

• HPMC treatment preserved TEER and reduced FITC-dextran leakage, indicating barrier stabilization.
• HPMC significantly suppressed the secretion of key inflammatory mediators.
• HPMC restored the expression and proper localization of TJ proteins zonula occludens-1 and occludin.
• HPMC attenuated NF-κB activation by inhibiting IκBα phosphorylation and nuclear translocation.

Conclusions:

• HPMC exhibits significant anti-inflammatory and barrier-stabilizing effects against cytokine-induced intestinal epithelial dysfunction.
• HPMC acts by restoring TJ integrity and inhibiting NF-κB signaling pathways.
• Non-cytotoxic HPMC demonstrates potential as a safe pharmaceutical excipient and functional dietary fiber for supporting intestinal health during inflammation.