{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:11:05Z","timestamp":1781932265491,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turku University Foundation","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"DOI":"10.13039\/501100005634","name":"Suomen Hammasl\u00e4\u00e4k\u00e4riseura Apollonia","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/501100005634","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Minerva Foundation, Finland","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"name":"National Science Foundation, USA","award":["CHE 2004102"],"award-info":[{"award-number":["CHE 2004102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on other periodontal cell types, such as gingival fibroblasts, remain to be clarified. The present aim was to examine the independent and combined effects of these cyclic dinucleotides and LPS on interleukin (IL) and matrix metalloproteinase (MMP) response of HGFs. The cells were incubated with c-di-GMP and c-di-AMP, either in the presence or absence of Porphyromonas gingivalis LPS, for 2 h and 24 h. The levels of IL-8, -10, and -34, and MMP-1, -2, and -3 secreted were measured by the Luminex technique. LPS alone or together with cyclic dinucleotides elevated IL-8 levels. IL-10 levels were significantly increased in the presence of c-di-GMP and LPS after 2 h but disappeared after 24 h of incubation. Concurrent treatment of c-di-AMP and LPS elevated MMP-1 levels, whereas c-di-GMP with LPS suppressed MMP-2 levels but increased MMP-3 levels. To conclude, we produce evidence that cyclic dinucleotides interact with LPS-mediated early response of gingival fibroblasts, while late cellular response is mainly regulated by LPS.<\/jats:p>","DOI":"10.3390\/pathogens9100792","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T22:24:42Z","timestamp":1601245482000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Activation of Gingival Fibroblasts by Bacterial Cyclic Dinucleotides and Lipopolysaccharide"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8641-2513","authenticated-orcid":false,"given":"Samira","family":"Elmanfi","sequence":"first","affiliation":[{"name":"Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman O.","family":"Sintim","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Purdue Institute for Drug Discovery and Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Purdue Institute for Drug Discovery and Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-6821","authenticated-orcid":false,"given":"Mervi","family":"G\u00fcrsoy","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija","family":"K\u00f6n\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland"},{"name":"Oral Health Care, Welfare Division, City of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-5751","authenticated-orcid":false,"given":"Ulvi K.","family":"G\u00fcrsoy","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1601-0825.1995.tb00193.x","article-title":"Origins and functions of cells essential for periodontal repair: The role of fibroblasts in tissue homeostasis","volume":"1","author":"McCulloch","year":"1995","journal-title":"Oral Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fcimb.2019.00262","article-title":"Pathogenesis of important virulence factors of Porphyromonas gingivalis via Toll-Like receptors","volume":"9","author":"Jia","year":"2019","journal-title":"Front. 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