Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice.

Abstract

Resveratrol is a polyphenol abundantly found in red grape skin and is effective against antiaging and anti-inflammation associated with immune responses. In this study, we have investigated the effect of resveratrol on skin lesion, high mobility group box (HMGB)1 and inflammation pathway in an atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga mouse. After AD induction, resveratrol (20 mg/kg, p.o.) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll like receptor (TLR)4, nuclear factor (NF)κB, phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, IL-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. Treatment of resveratrol inhibited the development of the AD-like skin lesions. Histological analysis showed that resveratrol inhibited hypertrophy, intracellular edema, mast cells and infiltration of inflammatory cells. Furthermore, resveratrol treatment down-regulated HMGB1, RAGE, p-NFκB, p-PI3K, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4. Considering all these findings together, the HMGB1 pathway might be a potential therapeutic target in skin inflammation, and resveratrol treatment could have beneficial effects on AD by modulating the HMGB1 protein expression.

• Authors: Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan A Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Mayumi Nomoto, Shizuka Miyashita, Kenji Suzuki, Kenichi Watanabe
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 23 Issue 2 Pg. 617-23 (Dec 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25466270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• HMGB1 Protein
• HMGB1 protein, mouse
• Stilbenes
• Resveratrol

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Cytokines (blood, immunology)
• Dermatitis, Atopic (drug therapy, etiology, immunology, pathology)
• Disease Models, Animal
• Female
• HMGB1 Protein (metabolism)
• Mice, Inbred Strains
• Pyroglyphidae (immunology)
• Resveratrol
• Severity of Illness Index
• Signal Transduction (drug effects, immunology)
• Skin (drug effects, immunology, pathology)
• Stilbenes (administration & dosage, therapeutic use)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)