Licoricidin Abrogates T-Cell Activation by Modulating PTPN1 Activity and Attenuates Atopic Dermatitis In Vivo.
J Invest Dermatol
; 141(10): 2490-2498.e6, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-33857487
ABSTRACT
Licoricidin, the fifth-highest fraction among the isolated 48 molecules from Glycyrrhiza uralensis extracts, has been known as an anti-inflammatory bioactive molecule; however, few studies have shown its inhibitory effect on T-cell activation and atopic dermatitis (AD). This study examined the therapeutic potential of licoricidin in AD by modulating T-cell activation with molecular mechanisms. Licoricidin attenuated the expression of IL-2 mRNA in stimulated T cells without cytotoxicity. Because tyrosine-protein phosphatase nonreceptor type 1 was predicted to interact physically with licoricidin in T cells in silico analysis, the results of tyrosine-protein phosphatase nonreceptor type 1 activity assay and phosphorylation study predicted that licoricidin might abrogate the activity of tyrosine-protein phosphatase nonreceptor type 1 during T-cell activation. Pretreatment with licoricidin controlled the dephosphorylation of Lck on TCR-mediated stimulation. Moreover, licoricidin alleviated the symptoms of dinitrochlorobenzene- and/or mite extract-induced AD, including ear thickness and serum IgE level. Microscopic analysis also showed the effects of licoricidin on the thickness of the dermis and epidermis and infiltration of immune cells. Furthermore, mRNA levels of proinflammatory cytokines were attenuated in the ear lesions of licoricidin-treated AD mice. Therefore, licoricidin has therapeutic potential for treating AD, and its underlying mechanism involves effective modulation of T-cell activation by controlling tyrosine-protein phosphatase nonreceptor type 1 to maintain Lck phosphorylation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzopiranos
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Activación de Linfocitos
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Linfocitos T
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Dermatitis Atópica
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Proteína Tirosina Fosfatasa no Receptora Tipo 1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article