HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.

<h4>Background and aims</h4>Patients with liver disease infected with the human immunodeficiency virus (HIV) exhibit accelerated progression of hepatic fibrosis and liver cirrhosis compared to uninfected individuals. We studied the effects of soluble factors secreted by HIV-infected peri...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Deepti Gupta, Manjusha Rani, Nabab Khan, Shahid Jameel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e814cf6b8ca405092b5a38e2b7dcda1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8e814cf6b8ca405092b5a38e2b7dcda1
record_format	dspace
spelling	oai:doaj.org-article:8e814cf6b8ca405092b5a38e2b7dcda12021-11-18T08:27:48ZHIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.1932-620310.1371/journal.pone.0091569https://doaj.org/article/8e814cf6b8ca405092b5a38e2b7dcda12014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24637780/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and aims</h4>Patients with liver disease infected with the human immunodeficiency virus (HIV) exhibit accelerated progression of hepatic fibrosis and liver cirrhosis compared to uninfected individuals. We studied the effects of soluble factors secreted by HIV-infected peripheral blood mononuclear cells (PBMCs) on hepatic stellate cells (HSCs), which are central mediators of liver fibrosis.<h4>Methods</h4>An in vitro model was used in which a HSC line, LX2, was treated with culture supernatants of human PBMCs infected with macrophage tropic (R5) or T cell tropic (X4) strains of HIV-1. Quantitative reverse transcription PCR (qRT-PCR) and western blotting were used to assess the expression of fibrogenic and proinflammatory markers; LX2 proliferation and intracellular signaling pathways were also studied. A qRT-PCR based miRNome array was used for comparative miRNA profiling of LX2 cells treated with infected PBMC culture supernatants.<h4>Results</h4>Pro-fibrogenic, angiogenic and proinflammatory markers, and proliferation of LX2 cells were increased following exposure to culture supernatants from HIV-1 infected PBMCs. The profiling of miRNAs in LX2 cells treated with culture supernatants from HIV-1 R5- or X4-infected PBMCs showed 66 and 22 miRNAs respectively, to be significantly altered compared to mock-treated LX2 cells. While different sets of miRNAs were altered in the two cases, bioinformatics analyses predicted these to be associated with common pathways, including TGF-β signaling and extracellular matrix receptor interaction pathways.<h4>Conclusions</h4>HIV infection creates a favorable milieu for the activation of hepatic stellate cells and increased hepatic fibrosis. We identify some regulatory molecules important for these effects.Deepti GuptaManjusha RaniNabab KhanShahid JameelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91569 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deepti Gupta Manjusha Rani Nabab Khan Shahid Jameel HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
description	<h4>Background and aims</h4>Patients with liver disease infected with the human immunodeficiency virus (HIV) exhibit accelerated progression of hepatic fibrosis and liver cirrhosis compared to uninfected individuals. We studied the effects of soluble factors secreted by HIV-infected peripheral blood mononuclear cells (PBMCs) on hepatic stellate cells (HSCs), which are central mediators of liver fibrosis.<h4>Methods</h4>An in vitro model was used in which a HSC line, LX2, was treated with culture supernatants of human PBMCs infected with macrophage tropic (R5) or T cell tropic (X4) strains of HIV-1. Quantitative reverse transcription PCR (qRT-PCR) and western blotting were used to assess the expression of fibrogenic and proinflammatory markers; LX2 proliferation and intracellular signaling pathways were also studied. A qRT-PCR based miRNome array was used for comparative miRNA profiling of LX2 cells treated with infected PBMC culture supernatants.<h4>Results</h4>Pro-fibrogenic, angiogenic and proinflammatory markers, and proliferation of LX2 cells were increased following exposure to culture supernatants from HIV-1 infected PBMCs. The profiling of miRNAs in LX2 cells treated with culture supernatants from HIV-1 R5- or X4-infected PBMCs showed 66 and 22 miRNAs respectively, to be significantly altered compared to mock-treated LX2 cells. While different sets of miRNAs were altered in the two cases, bioinformatics analyses predicted these to be associated with common pathways, including TGF-β signaling and extracellular matrix receptor interaction pathways.<h4>Conclusions</h4>HIV infection creates a favorable milieu for the activation of hepatic stellate cells and increased hepatic fibrosis. We identify some regulatory molecules important for these effects.
format	article
author	Deepti Gupta Manjusha Rani Nabab Khan Shahid Jameel
author_facet	Deepti Gupta Manjusha Rani Nabab Khan Shahid Jameel
author_sort	Deepti Gupta
title	HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
title_short	HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
title_full	HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
title_fullStr	HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
title_full_unstemmed	HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.
title_sort	hiv-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted tgf-β and jnk signaling.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8e814cf6b8ca405092b5a38e2b7dcda1
work_keys_str_mv	AT deeptigupta hiv1infectedperipheralbloodmononuclearcellsmodulatethefibrogenicactivityofhepaticstellatecellsthroughsecretedtgfbandjnksignaling AT manjusharani hiv1infectedperipheralbloodmononuclearcellsmodulatethefibrogenicactivityofhepaticstellatecellsthroughsecretedtgfbandjnksignaling AT nababkhan hiv1infectedperipheralbloodmononuclearcellsmodulatethefibrogenicactivityofhepaticstellatecellsthroughsecretedtgfbandjnksignaling AT shahidjameel hiv1infectedperipheralbloodmononuclearcellsmodulatethefibrogenicactivityofhepaticstellatecellsthroughsecretedtgfbandjnksignaling
_version_	1718421754806796288

HIV-1 infected peripheral blood mononuclear cells modulate the fibrogenic activity of hepatic stellate cells through secreted TGF-β and JNK signaling.

Ejemplares similares