hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis

Abstract In periodontitis, gingival fibroblasts (GFs) interact with and respond to oral pathogens, significantly contributing to perpetuation of chronic inflammation and tissue destruction. The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) ce...

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Autores principales:	Katarzyna B. Lagosz-Cwik, Aleksandra Wielento, Weronika Lipska, Malgorzata Kantorowicz, Dagmara Darczuk, Tomasz Kaczmarzyk, Susan Gibbs, Jan Potempa, Aleksander M. Grabiec
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1188639df7849ddb2f8c5a9c0c06082
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spelling	oai:doaj.org-article:f1188639df7849ddb2f8c5a9c0c060822021-12-02T15:00:55ZhTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis10.1038/s41598-021-90037-52045-2322https://doaj.org/article/f1188639df7849ddb2f8c5a9c0c060822021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90037-5https://doaj.org/toc/2045-2322Abstract In periodontitis, gingival fibroblasts (GFs) interact with and respond to oral pathogens, significantly contributing to perpetuation of chronic inflammation and tissue destruction. The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) cell line for studies of host–pathogen interactions. We show that TIGFs are unable to upregulate expression and production of interleukin (IL)-6, IL-8 and prostaglandin E2 upon infection with Porphyromonas gingivalis despite being susceptible to adhesion and invasion by this oral pathogen. In contrast, induction of inflammatory mediators in TNFα- or IL-1β-stimulated TIGFs is comparable to that observed in primary GFs. The inability of TIGFs to respond directly to P. gingivalis is caused by a specific defect in Toll-like receptor-2 (TLR2) expression, which is likely driven by TLR2 promoter hypermethylation. Consistently, TIGFs fail to upregulate inflammatory genes in response to the TLR2 agonists Pam2CSK4 and Pam3CSK4. These results identify important limitations of using TIGFs to study GF interaction with oral pathogens, though these cells may be useful for studies of TLR2-independent processes. Our observations also emphasize the importance of direct comparisons between immortalized and primary cells prior to using cell lines as models in studies of any biological processes.Katarzyna B. Lagosz-CwikAleksandra WielentoWeronika LipskaMalgorzata KantorowiczDagmara DarczukTomasz KaczmarzykSusan GibbsJan PotempaAleksander M. GrabiecNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katarzyna B. Lagosz-Cwik Aleksandra Wielento Weronika Lipska Malgorzata Kantorowicz Dagmara Darczuk Tomasz Kaczmarzyk Susan Gibbs Jan Potempa Aleksander M. Grabiec hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
description	Abstract In periodontitis, gingival fibroblasts (GFs) interact with and respond to oral pathogens, significantly contributing to perpetuation of chronic inflammation and tissue destruction. The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) cell line for studies of host–pathogen interactions. We show that TIGFs are unable to upregulate expression and production of interleukin (IL)-6, IL-8 and prostaglandin E2 upon infection with Porphyromonas gingivalis despite being susceptible to adhesion and invasion by this oral pathogen. In contrast, induction of inflammatory mediators in TNFα- or IL-1β-stimulated TIGFs is comparable to that observed in primary GFs. The inability of TIGFs to respond directly to P. gingivalis is caused by a specific defect in Toll-like receptor-2 (TLR2) expression, which is likely driven by TLR2 promoter hypermethylation. Consistently, TIGFs fail to upregulate inflammatory genes in response to the TLR2 agonists Pam2CSK4 and Pam3CSK4. These results identify important limitations of using TIGFs to study GF interaction with oral pathogens, though these cells may be useful for studies of TLR2-independent processes. Our observations also emphasize the importance of direct comparisons between immortalized and primary cells prior to using cell lines as models in studies of any biological processes.
format	article
author	Katarzyna B. Lagosz-Cwik Aleksandra Wielento Weronika Lipska Malgorzata Kantorowicz Dagmara Darczuk Tomasz Kaczmarzyk Susan Gibbs Jan Potempa Aleksander M. Grabiec
author_facet	Katarzyna B. Lagosz-Cwik Aleksandra Wielento Weronika Lipska Malgorzata Kantorowicz Dagmara Darczuk Tomasz Kaczmarzyk Susan Gibbs Jan Potempa Aleksander M. Grabiec
author_sort	Katarzyna B. Lagosz-Cwik
title	hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
title_short	hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
title_full	hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
title_fullStr	hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
title_full_unstemmed	hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
title_sort	htert-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to porphyromonas gingivalis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f1188639df7849ddb2f8c5a9c0c06082
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hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis

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