Ribes nigrum L. (blackcurrant) leaf extracts, due to high levels of flavonols and anthocyanins, have been shown to exhibit beneficial effects in inflammatory diseases. However, whereas their traditional use has been investigated and validated in several models of inflammation and oxidative stress, the possible impact on skin disorders is still largely unknown. The purpose of this work was to elucidate the effects of R. nigrum leaf extract (RNLE) on keratinocyte-derived inflammatory mediators, elicited by a Th1 or Th2 cytokine milieu. HaCaT cells were challenged with TNF-alpha, either alone or in combination with the costimulatory cytokines IFN-gamma or IL-4, and the release of proinflammatory cytokines and mediators (IL-8, IL-6, s-ICAM-1, and TSLP) was evaluated. The results showed that RNLE preferentially interferes with IFN-signaling, demonstrating only negligible activity on TNF-alpha or IL-4. This effect was attributed to flavonols, which might also account for the ability of RNLE to impair TNF-alpha/IL-4-induced TSLP release in a cAMP-independent manner. These results suggest that RNLE could have an antiallergic effect mediated in keratinocytes via mechanisms beyond histamine involvement. In conclusion, the discovery of RNLE preferential activity against IFN-gamma mediated inflammation suggests potential selectivity against Th1 type response and the possible use in Th1 inflammatory diseases.

Ribes nigrum Leaf Extract Preferentially Inhibits IFN-γ-Mediated Inflammation in HaCaT Keratinocytes / A. Magnavacca, S. Piazza, A. Cammisa, M. Fumagalli, G. Martinelli, F. Giavarini, E. Sangiovanni, M. Dell’Agli. - In: MOLECULES. - ISSN 1420-3049. - 26:10(2021 May 20), pp. 3044.1-3044.23. [10.3390/molecules26103044]

Ribes nigrum Leaf Extract Preferentially Inhibits IFN-γ-Mediated Inflammation in HaCaT Keratinocytes

A. Magnavacca
Co-primo
;
S. Piazza
Co-primo
;
M. Fumagalli;G. Martinelli;F. Giavarini;E. Sangiovanni
Penultimo
;
M. Dell’Agli
Ultimo
2021-05-20

Abstract

Ribes nigrum L. (blackcurrant) leaf extracts, due to high levels of flavonols and anthocyanins, have been shown to exhibit beneficial effects in inflammatory diseases. However, whereas their traditional use has been investigated and validated in several models of inflammation and oxidative stress, the possible impact on skin disorders is still largely unknown. The purpose of this work was to elucidate the effects of R. nigrum leaf extract (RNLE) on keratinocyte-derived inflammatory mediators, elicited by a Th1 or Th2 cytokine milieu. HaCaT cells were challenged with TNF-alpha, either alone or in combination with the costimulatory cytokines IFN-gamma or IL-4, and the release of proinflammatory cytokines and mediators (IL-8, IL-6, s-ICAM-1, and TSLP) was evaluated. The results showed that RNLE preferentially interferes with IFN-signaling, demonstrating only negligible activity on TNF-alpha or IL-4. This effect was attributed to flavonols, which might also account for the ability of RNLE to impair TNF-alpha/IL-4-induced TSLP release in a cAMP-independent manner. These results suggest that RNLE could have an antiallergic effect mediated in keratinocytes via mechanisms beyond histamine involvement. In conclusion, the discovery of RNLE preferential activity against IFN-gamma mediated inflammation suggests potential selectivity against Th1 type response and the possible use in Th1 inflammatory diseases.
Ribes nigrum; blackcurrant leaves; skin; inflammation; keratinocytes; IFN-gamma; TSLP
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/845175
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