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oai:gupea.ub.gu.se:2077/528412017-09-28T01:39:49Zcom_2077_280com_2077_17com_2077_10556col_2077_545col_2077_310col_2077_10557

Basic, Amina 2017-09-27T13:40:24Z 2017-09-27T13:40:24Z 2017-09-27 978-91-629-0270-4 (print) 978-91-629-0271-1 (pdf) http://hdl.handle.net/2077/52841 Hydrogen sulfide (H2S) is one of many end-products of the proteolytic activities in the subgingival microbiota in patients with periodontal diseases, such as gingivitis and periodontitis. Although H2S is generally regarded as toxic, the mechanisms that underlie its production and its effects on human cells and tissues are poorly understood. Therefore, the role of H2S in the pathogenesis of periodontal diseases was investigated. Two colorimetric methods, the bismuth test (BT) and the methylene blue (MB) method, were used to estimate the amounts of H2S produced by the bacteria in vitro and ex vivo (Papers I, II and V). Oral bacteria, e.g., Fusobacterium spp., Porphyromonas gingivalis and Treponema denticola, were found to have strong capacities to degrade cysteine and produce H2S in vitro (Paper I). The Fusobacterium spp. were found to express several enzymes that are involved in the production of H2S. The expression patterns of the different enzymes varied among Fusobacterium subspecies and strains (Paper III). In an ex vivo experiment using BT, we showed that the subgingival plaques of subjects (N=43) with poor oral hygiene had the capacity to produce H2S (Paper II). High levels of periodontitis-associated bacteria were detected, and the BT values reflected the proteolytic activities of the bacteria and gingival inflammation rather than disease progression and periodontitis. A correlation between a positive BT and gingival inflammation was confirmed in Paper V, where H2S-producing bacteria were significantly more prevalent in the subgingival pockets of periodontitis patients (N=32) than of healthy controls (N=32), which indicates potent bacterial proteolytic activities in the untreated deep periodontal pockets. Paper IV described how the peripheral blood mononuclear cells (PBMCs) of blood donors and a monocytic cell line increased their secretion of the pro-inflammatory cytokines IL-1β and IL-18 in vitro when exposed to the H2S-donor sodium hydrosulfide (NaHS). This secretion was shown to be mediated by the NLRP3 inflammasome. These results were verified in Paper V, where the PBMCs of periodontitis patients and healthy controls secreted significantly higher levels of IL-1β and IL-18 when exposed to NaHS. In addition, both unexposed and exposed PBMCs of the periodontitis patients secreted higher levels of the two cytokines than the corresponding cells of healthy controls. These results suggest that the susceptibility of the host to develop disease can be attributed in part to enhanced secretion of pro-inflammatory cytokines following exposure to bacterial metabolites, such as H2S. In summary, toxic bacterial metabolites, such as H2S, may play an important role by affecting the cells of the host immune system, thereby inducing and sustaining gingival inflammation. eng I. Basic A, Blomqvist S, Carlén A, Dahlén G. Estimation of bacterial hydrogen sulfide production in vitro. Journal of Oral Microbiology 7. 2015. ::doi::10.3402/jom.v7.28166 II. Basic A, Dahlén G. Hydrogen sulfide production from subgingival plaque samples. Anaerobe 35:21-27. 2015. ::doi::10.1016/j.anaerobe.2014.09.017 III. Basic A, Blomqvist M, Dahlén G, Svensäter G. The proteins of Fusobacterium spp. involved in hydrogen sulfide production from L-cysteine. BMC Microbiology 17. 2017. ::doi::10.1186/s12866-017-0967-9 IV. Basic A, Alizadehgharib S, Dahlén G, Dahlgren U. Hydrogen sulfide exposure induces NLRP3 inflammasome-dependent IL-1β and IL-18 secretion in human mononuclear leukocytes in vitro. Clinical and Experimental Dental Research 3:115-120. 2017 ::doi::10.1002/cre2.69 V. Basic A, Serino G, Leonhardt Å, Dahlén G Induction of interleukin (IL)-1β and IL-18 secretion by hydrogen sulfide in periodontitis patients and healthy controls: a clinical cross-sectional study In manuscript Hydrogen sulfide Periodontitis Gingivitis IL-1β IL-18 NLRP3 inflammasome Oral microbiota Fusobacterium spp. Bismuth test L-cysteine Importance of bacterial hydrogen sulfide in the pathogenesis of periodontal diseases Text Doctoral thesis Doctor of Philosophy (Odontology) amina.basic@gu.se University of Gothenburg. Sahlgrenska Academy Institute of Odontology. Department of Oral Microbiology Fredagen den 20 oktober 2017, kl. 9.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborg 2017-10-20 SA open.access