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-alpha, IL6, IL-1 beta, and IL-8 in HSFs treated with LPS. However, treatment with GA significantly decreased levels of TNF-alpha, IL-6, IL-1 beta, and IL-8 in HSFs. Results also show that LPS reduced both PPAR gamma mRNA and protein expression in HSFs, but GA can upregulate expression of PPAR gamma and downregulate expression of TLR-4. Results indicate that LPS negatively regulates expression of PPAR gamma in HSFs but GA can antagonize these effects of LPS. Furthermore, LPS-induced inhibition of PPAR gamma was not observed in HSFs treated with a TLR-4 siRNA. Additionally, overexpression TLR-4 can induce the inhibition of PPAR gamma, but GA can increase PPAR gamma expression in HSFs that have been engineered to overexpress TLR-4. This study further proved that GA can significantly inhibit LPS-induced NF-kappa B expression. Results indicate that GA has a positive effect on HTS by attenuating LPS induced inflammatory response via TLR-4/NF-kappa B/PPAR gamma 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.