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The process is responsible for proper membrane localization and the appropriate function of several intracellular signaling proteins. Current research demonstrating the pathomechanistic importance of prenylation in inflammatory illnesses emphasizes the requirement to ascertain the differential expression of PT genes under inflammatory settings, particularly in periodontal disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Telomerase\u2010immortalized human gingival fibroblasts (HGF\u2010hTert) were cultured and treated with either inhibitors of prenylation (PTI) lonafarnib, tipifarnib, zoledronic acid, or atorvastatin at concentrations of 10 \u03bcM in combination with or without 10\u00a0\u03bcg <jats:italic>Porphyromonas gingivalis<\/jats:italic> lipopolysaccharide (LPS) for 24\u00a0h. Prenyltransferase genes <jats:italic>FNTB, FNTA, PGGT1B, RABGGTA, RABGGTB<\/jats:italic>, and <jats:italic>PTAR1<\/jats:italic> as well as inflammatory marker genes <jats:italic>MMP1<\/jats:italic> and <jats:italic>IL1B<\/jats:italic> were detected using quantitative real\u2010time polymerase chain reaction (RT\u2010qPCR). Immunoblot and protein immunoassay were used to confirm the results on the protein level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RT\u2010qPCR experiments revealed significant upregulation of <jats:italic>IL1B<\/jats:italic>, <jats:italic>MMP1, FNTA<\/jats:italic>, and <jats:italic>PGGT1B<\/jats:italic> upon LPS treatment. PTase inhibitors caused significant downregulation of the inflammatory cytokine expression. Interestingly, <jats:italic>FNTB<\/jats:italic> expression was significantly upregulated in response to any PTase inhibitor in combination with LPS, but not upon LPS treatment only, indicating a vital role of protein farnesyltransferase in the proinflammatory signaling cascade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, distinct PTase gene expression patterns in pro\u2010inflammatory signaling were discovered. Moreover, PTase inhibiting drugs ameliorated inflammatory mediator expression by a significant margin, indicating that prenylation is a major pre\u2010requisite for innate immunity in periodontal cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.23-0220","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T13:32:01Z","timestamp":1689082321000},"page":"1450-1460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prenyltransferase gene expression reveals an essential role of prenylation for the inflammatory response in human gingival fibroblasts"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-3823","authenticated-orcid":false,"given":"Daniel","family":"Diehl","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology Center for Biomedical Education and Research (ZBAF) Faculty of Health Witten\/Herdecke University 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