Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes

Summary: Psoriasis is a chronic skin disease, in which immune cells and keratinocytes keep each other in a state of inflammation. It is believed that phospholipase A2 (PLA2)-dependent eicosanoid release plays a key role in this. T-helper (Th) 1-derived cytokines are established activators of phospho...

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Autores principales:	Eirini Tsirvouli, Felicity Ashcroft, Berit Johansen, Martin Kuiper
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Dermatology Systems biology Experimental models in systems biology Science Q
Acceso en línea:	https://doaj.org/article/4bc0bef92b5a41eba07fd5930063ec08
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spelling	oai:doaj.org-article:4bc0bef92b5a41eba07fd5930063ec082021-11-28T04:36:40ZLogical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes2589-004210.1016/j.isci.2021.103451https://doaj.org/article/4bc0bef92b5a41eba07fd5930063ec082021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101422Xhttps://doaj.org/toc/2589-0042Summary: Psoriasis is a chronic skin disease, in which immune cells and keratinocytes keep each other in a state of inflammation. It is believed that phospholipase A2 (PLA2)-dependent eicosanoid release plays a key role in this. T-helper (Th) 1-derived cytokines are established activators of phospholipases in keratinocytes, whereas Th17-derived cytokines have largely unknown effects. Logical model simulations describing the function of cytokine and eicosanoid signaling networks combined with experimental data suggest that Th17 cytokines stimulate proinflammatory cytokine expression in psoriatic keratinocytes via activation of cPLA2α-Prostaglandin E2-EP4 signaling, which could be suppressed using the anti-psoriatic calcipotriol. cPLA2α inhibition and calcipotriol distinctly regulate expression of key psoriatic genes, possibly offering therapeutic advantage when applied together. Model simulations additionally suggest EP4 and protein kinase cAMP-activated catalytic subunit alpha as drug targets that may restore a normal phenotype. Our work illustrates how the study of complex diseases can benefit from an integrated systems approach.Eirini TsirvouliFelicity AshcroftBerit JohansenMartin KuiperElsevierarticleDermatologySystems biologyExperimental models in systems biologyScienceQENiScience, Vol 24, Iss 12, Pp 103451- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dermatology Systems biology Experimental models in systems biology Science Q
spellingShingle	Dermatology Systems biology Experimental models in systems biology Science Q Eirini Tsirvouli Felicity Ashcroft Berit Johansen Martin Kuiper Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
description	Summary: Psoriasis is a chronic skin disease, in which immune cells and keratinocytes keep each other in a state of inflammation. It is believed that phospholipase A2 (PLA2)-dependent eicosanoid release plays a key role in this. T-helper (Th) 1-derived cytokines are established activators of phospholipases in keratinocytes, whereas Th17-derived cytokines have largely unknown effects. Logical model simulations describing the function of cytokine and eicosanoid signaling networks combined with experimental data suggest that Th17 cytokines stimulate proinflammatory cytokine expression in psoriatic keratinocytes via activation of cPLA2α-Prostaglandin E2-EP4 signaling, which could be suppressed using the anti-psoriatic calcipotriol. cPLA2α inhibition and calcipotriol distinctly regulate expression of key psoriatic genes, possibly offering therapeutic advantage when applied together. Model simulations additionally suggest EP4 and protein kinase cAMP-activated catalytic subunit alpha as drug targets that may restore a normal phenotype. Our work illustrates how the study of complex diseases can benefit from an integrated systems approach.
format	article
author	Eirini Tsirvouli Felicity Ashcroft Berit Johansen Martin Kuiper
author_facet	Eirini Tsirvouli Felicity Ashcroft Berit Johansen Martin Kuiper
author_sort	Eirini Tsirvouli
title	Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
title_short	Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
title_full	Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
title_fullStr	Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
title_full_unstemmed	Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
title_sort	logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4bc0bef92b5a41eba07fd5930063ec08
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_version_	1718408256548765696

Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes

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