Premium
Modulation of HMGB 1 translocation and RAGE / NF κ B cascade by quercetin treatment mitigates atopic dermatitis in NC /Nga transgenic mice
Author(s) -
Karuppagounder Vengadeshprabhu,
Arumugam Somasundaram,
Thandavarayan Rajarajan A.,
Pitchaimani Vigneshwaran,
Sreedhar Remya,
Afrin Rejina,
Harima Meilei,
Suzuki Hiroshi,
Nomoto Mayumi,
Miyashita Shizuka,
Suzuki Kenji,
Nakamura Masahiko,
Watanabe Kenichi
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12685
Subject(s) - inflammation , rage (emotion) , tumor necrosis factor alpha , hmgb1 , chemistry , immunology , microbiology and biotechnology , pharmacology , medicine , biology , neuroscience
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 HMGB 1, receptor for advanced glycation end products ( RAGE ), toll‐like receptor ( TLR )4, nuclear factor ( NF ) κ B, 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 )‐1 β , IL ‐2R α 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 HMGB 1, RAGE , nuclear p‐ NF κ B, p‐ ERK 1/2, COX 2, TNF α , IL ‐1 β , IL ‐2R α , IFN γ and IL ‐4 and upregulated nuclear Nrf2. Our data demonstrated that the HMGB 1/ RAGE / NF κ B signalling might play an important role in skin inflammation, and quercetin treatment could be a promising agent for AD by modulating the HMGB 1/ RAGE / NF κ B signalling and induction of Nrf2 protein.