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Therapeutic effect of kaempferol on atopic dermatitis by attenuation of T cell activity via interaction with multidrug resistance-associated protein 1.

Authors :
Lee, Hyun‐Su
Jeong, Gil‐Saeng
Lee, Hyun-Su
Jeong, Gil-Saeng
Source :
British Journal of Pharmacology; Apr2021, Vol. 178 Issue 8, p1772-1788, 17p, 2 Color Photographs, 3 Black and White Photographs, 2 Diagrams, 1 Chart, 2 Graphs
Publication Year :
2021

Abstract

<bold>Background and Purpose: </bold>Kaempferol is a natural flavonoid widely investigated in various fields due to its antioxidant, anti-cancer, and anti-inflammatory activities, but few studies have shown its inhibitory effect on T cell activation. This study examined the therapeutic potential of kaempferol in atopic dermatitis by modulating T cell activation.<bold>Experimental Approach: </bold>Effects of kaempferol on T cell activation and the underlying mechanisms were investigated in Jurkat cells and mouse CD4+ T cells. A model of atopic dermatitis in mice was used to determine its therapeutic potential on T cell-mediated conditions in vivo. Western blots, RT-PCR, pulldown assays and ELISA were used, along with histological analysis of skin.<bold>Key Results: </bold>Pretreatment with kaempferol reduced CD69 expression and production of inflammatory cytokines including IL-2 from activated Jurkat cells and murine CD4+ T cells without cytotoxicity. Pulldown assays revealed that kaempferol physically binds to MRP-1 in T cells, inhibiting the action of MRP-1. In activated T cells, kaempferol suppressed JNK phosphorylation and the TAK1-IKKα mediated NF-κB pathway. Oral administration of kaempferol to mice showed improved manifestation of atopic dermatitis, a T cell-mediated condition. Western blot results showed that, as in the in vitro studies, decreased phosphorylation of JNK was associated with down-regulated MRP-1 activity in vivo, in the kaempferol-treated mice in the atopic dermatitis model.<bold>Conclusion and Implications: </bold>Kaempferol regulates T cell activation by inhibiting MRP-1 activity in activated T cells, thus showing protective effects against T cell mediated disease in vivo. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00071188
Volume :
178
Issue :
8
Database :
Complementary Index
Journal :
British Journal of Pharmacology
Publication Type :
Academic Journal
Accession number :
149399325
Full Text :
https://doi.org/10.1111/bph.15396