Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.

Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte hyperproliferation and chronic inflammation, with increased expression of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF). Anti-TNF biologic agents are effective in treating Ps, but are associated with in...

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Autores principales:	Zuyi Weng, Arti B Patel, Magdalini Vasiadi, Anastasia Therianou, Theoharis C Theoharides
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a3d9bad55b94ab88ee8e05d916b0700
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spelling	oai:doaj.org-article:8a3d9bad55b94ab88ee8e05d916b07002021-11-18T08:30:12ZLuteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.1932-620310.1371/journal.pone.0090739https://doaj.org/article/8a3d9bad55b94ab88ee8e05d916b07002014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587411/?tool=EBIhttps://doaj.org/toc/1932-6203Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte hyperproliferation and chronic inflammation, with increased expression of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF). Anti-TNF biologic agents are effective in treating Ps, but are associated with increased risk of infections and blood malignancies. Moreover, keratinocyte hyperproliferation and activation have yet to be addressed. Flavonoids, such as luteolin, are natural compounds with potent anti-inflammatory properties, but their actions on keratinocytes remain unknown. We show that TNF (50 ng/mL) triggers significant production of inflammatory mediators interleukin-6, interleukin-8 and VEGF from both human HaCaT and primary keratinocytes. Pretreatment with the flavonoid luteolin (10-100 µM) significantly inhibits mRNA expression and release of all three mediators in a concentration-dependent manner. More importantly, luteolin decreases TNF-induced phosphorylation, nuclear translocation and DNA binding of the nuclear factor-kappa B (NF-κB) typically involved in inflammatory mediator transcription. We also report that luteolin reduces TNF-induced mRNA expression of two genes (NFKB1 and RELA) encoding two NF-κB subunits (NF-κB p50 and NF-κB p65, respectively). Interestingly, we show that gene expression of RELA is increased in human psoriatic skin. Keratinocyte proliferation, which is a characteristic feature of psoriatic skin, is effectively reduced by luteolin in HaCaT cells, but not in primary keratinocytes. Finally, luteolin does not affect intracellular ATP production or viability. Appropriate formulations of luteolin and related flavones may be promising candidates to be developed into local and systemic treatments for Ps and other inflammatory skin diseases.Zuyi WengArti B PatelMagdalini VasiadiAnastasia TherianouTheoharis C TheoharidesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e90739 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zuyi Weng Arti B Patel Magdalini Vasiadi Anastasia Therianou Theoharis C Theoharides Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
description	Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte hyperproliferation and chronic inflammation, with increased expression of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF). Anti-TNF biologic agents are effective in treating Ps, but are associated with increased risk of infections and blood malignancies. Moreover, keratinocyte hyperproliferation and activation have yet to be addressed. Flavonoids, such as luteolin, are natural compounds with potent anti-inflammatory properties, but their actions on keratinocytes remain unknown. We show that TNF (50 ng/mL) triggers significant production of inflammatory mediators interleukin-6, interleukin-8 and VEGF from both human HaCaT and primary keratinocytes. Pretreatment with the flavonoid luteolin (10-100 µM) significantly inhibits mRNA expression and release of all three mediators in a concentration-dependent manner. More importantly, luteolin decreases TNF-induced phosphorylation, nuclear translocation and DNA binding of the nuclear factor-kappa B (NF-κB) typically involved in inflammatory mediator transcription. We also report that luteolin reduces TNF-induced mRNA expression of two genes (NFKB1 and RELA) encoding two NF-κB subunits (NF-κB p50 and NF-κB p65, respectively). Interestingly, we show that gene expression of RELA is increased in human psoriatic skin. Keratinocyte proliferation, which is a characteristic feature of psoriatic skin, is effectively reduced by luteolin in HaCaT cells, but not in primary keratinocytes. Finally, luteolin does not affect intracellular ATP production or viability. Appropriate formulations of luteolin and related flavones may be promising candidates to be developed into local and systemic treatments for Ps and other inflammatory skin diseases.
format	article
author	Zuyi Weng Arti B Patel Magdalini Vasiadi Anastasia Therianou Theoharis C Theoharides
author_facet	Zuyi Weng Arti B Patel Magdalini Vasiadi Anastasia Therianou Theoharis C Theoharides
author_sort	Zuyi Weng
title	Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
title_short	Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
title_full	Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
title_fullStr	Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
title_full_unstemmed	Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.
title_sort	luteolin inhibits human keratinocyte activation and decreases nf-κb induction that is increased in psoriatic skin.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8a3d9bad55b94ab88ee8e05d916b0700
work_keys_str_mv	AT zuyiweng luteolininhibitshumankeratinocyteactivationanddecreasesnfkbinductionthatisincreasedinpsoriaticskin AT artibpatel luteolininhibitshumankeratinocyteactivationanddecreasesnfkbinductionthatisincreasedinpsoriaticskin AT magdalinivasiadi luteolininhibitshumankeratinocyteactivationanddecreasesnfkbinductionthatisincreasedinpsoriaticskin AT anastasiatherianou luteolininhibitshumankeratinocyteactivationanddecreasesnfkbinductionthatisincreasedinpsoriaticskin AT theoharisctheoharides luteolininhibitshumankeratinocyteactivationanddecreasesnfkbinductionthatisincreasedinpsoriaticskin
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Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin.

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