title: 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.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Pitchaimani
authors.forename: Remya
authors.initials: R
authors.lastname: Sreedhar
authors.forename: Rejina
authors.initials: R
authors.lastname: Afrin
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nomoto
authors.forename: Shizuka
authors.initials: S
authors.lastname: Miyashita
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D008815:Mice, Inbred Strains; D039981:Pyroglyphidae / Q000276:immunology*; D000077185:Resveratrol; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D013267:Stilbenes; D000077185:Resveratrol