Gallic acid inhibits LPS induced hypertrophic scar inflammation via toll-like receptor 4 / nuclear factor-κB / peroxisome proliferator-activated receptor γ signaling

Prolonged and enhanced inflammation is a common pathogenic feature of hypertrophic scars (HTS). Gallic acid (GA) is a naturally occurring plant phenol with lots of pharmacological activities, including antimicrobial, anti-inflammatory, anticancer, antioxidant, and anti-fibrosis effects. The objective of this study was to evaluate the effects of GA in LPS induced inflammatory response. Results suggest that there is significant production of TNF-α, IL6, IL-1β, and IL-8 in HSFs treated with LPS. However, treatment with GA significantly decreased levels of TNF-α, IL-6, IL-1β, and IL-8 in HSFs. Results also show that LPS reduced both PPARγ mRNA and protein expression in HSFs, but GA can upregulate expression of PPARγ and downregulate expression of TLR-4. Results indicate that LPS negatively regulates expression of PPARγ in HSFs but GA can antagonize these effects of LPS. Furthermore, LPS-induced inhibition of PPARγ was not observed in HSFs treated with a TLR-4 siRNA. Additionally, overexpression TLR-4 can induce the inhibition of PPARγ, but GA can increase PPARγ expression in HSFs that have been engineered to overexpress TLR-4. This study further proved that GA can significantly inhibit LPS-induced NF-κB expression. Results indicate that GA has a positive effect on HTS by attenuating LPS induced inflammatory response via TLR-4/NF-κB/PPARγ signaling. Results also suggest a novel potential role for GA, which can be used as an effective drug for treatment of hypertrophic scars, keloids, and so forth.