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The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) cell line for studies of host\u2013pathogen interactions. We show that TIGFs are unable to upregulate expression and production of interleukin (IL)-6, IL-8 and prostaglandin E2 upon infection with <jats:italic>Porphyromonas gingivalis<\/jats:italic> despite being susceptible to adhesion and invasion by this oral pathogen. In contrast, induction of inflammatory mediators in TNF\u03b1- or IL-1\u03b2-stimulated TIGFs is comparable to that observed in primary GFs. The inability of TIGFs to respond directly to <jats:italic>P. gingivalis<\/jats:italic> is caused by a specific defect in Toll-like receptor-2 (TLR2) expression, which is likely driven by <jats:italic>TLR2<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-021-90037-5","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T10:02:53Z","timestamp":1621850573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis"],"prefix":"10.1038","volume":"11","author":[{"given":"Katarzyna B.","family":"Lagosz-Cwik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Wielento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Lipska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Kantorowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmara","family":"Darczuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Kaczmarzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander M.","family":"Grabiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"90037_CR1","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/s41590-020-0741-2","volume":"21","author":"V Koliaraki","year":"2020","unstructured":"Koliaraki, V., Prados, A., Armaka, M. & Kollias, G. 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