Modulation of HMGB1 translocation and RAGE/NFκB cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice

Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan A. Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Mayumi Nomoto, Shizuka Miyashita, Kenji Suzuki, Masahiko Nakamura, Kenichi Watanabe

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Quercetin, glycosylated form of flavonoid compound, has potent antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of quercetin on skin lesion, high-mobility group box (HMGB)1 cascade signalling and inflammation in 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 transgenic mouse. After AD induction, quercetin (50 mg/kg, p.o) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes 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, nuclear factor erythroid-2-related factor (Nrf)2, kelch-like ECH-associated protein (Keap)1, extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, IL-4) were measured by enzyme-linked immunosorbent assay. Quercetin treatment attenuated the development of AD-like skin lesions. Histological analysis showed that quercetin inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells. Furthermore, quercetin treatment downregulated cytoplasmic HMGB1, RAGE, nuclear p-NFκB, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4 and upregulated nuclear Nrf2. Our data demonstrated that the HMGB1/RAGE/NFκB signalling might play an important role in skin inflammation, and quercetin treatment could be a promising agent for AD by modulating the HMGB1/RAGE/NFκB signalling and induction of Nrf2 protein.

Original languageEnglish (US)
Pages (from-to)418-423
Number of pages6
JournalExperimental Dermatology
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Cytokine
  • High-mobility group box protein 1
  • Nuclear factor kappa B
  • Quercetin
  • Receptor for advanced glycation products

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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