PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production

Abstract HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and the...

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Autores principales:	Manutea Serrero, Rémi Planès, Elmostafa Bahraoui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6e1b3c7f25d7465198c5feda022d9a17
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spelling	oai:doaj.org-article:6e1b3c7f25d7465198c5feda022d9a172021-12-02T16:06:32ZPKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production10.1038/s41598-017-02468-82045-2322https://doaj.org/article/6e1b3c7f25d7465198c5feda022d9a172017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02468-8https://doaj.org/toc/2045-2322Abstract HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation. The finding that comparable amounts of CXCL8 were produced following stimulation with either Tat protein, PKC-delta CAT transfection, or both, argue for the implication of one common pathway where PKC delta is activated downstream of TLR4 recruitment and leads to the activation of NF-κB. Altogether, our results underline the crucial role of PKC delta isoform in activating gene expression of CXCL8, a cytokine largely implicated in the physiopathology of HIV-1 infection.Manutea SerreroRémi PlanèsElmostafa BahraouiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manutea Serrero Rémi Planès Elmostafa Bahraoui PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
description	Abstract HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation. The finding that comparable amounts of CXCL8 were produced following stimulation with either Tat protein, PKC-delta CAT transfection, or both, argue for the implication of one common pathway where PKC delta is activated downstream of TLR4 recruitment and leads to the activation of NF-κB. Altogether, our results underline the crucial role of PKC delta isoform in activating gene expression of CXCL8, a cytokine largely implicated in the physiopathology of HIV-1 infection.
format	article
author	Manutea Serrero Rémi Planès Elmostafa Bahraoui
author_facet	Manutea Serrero Rémi Planès Elmostafa Bahraoui
author_sort	Manutea Serrero
title	PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
title_short	PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
title_full	PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
title_fullStr	PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
title_full_unstemmed	PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
title_sort	pkc-δ isoform plays a crucial role in tat-tlr4 signalling pathway to activate nf-κb and cxcl8 production
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6e1b3c7f25d7465198c5feda022d9a17
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_version_	1718384966970114048

PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production

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