Browsing by Subject "Treponema denticola"

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  • Kylmä, Anna Kaisa; Jouhi, Lauri; Mohamed, Hesham; Randen-Brady, Reija; Mäkitie, Antti; Atula, Timo; Haglund, Caj; Sorsa, Timo; Hagström, Jaana (2020)
    Objectives: In oropharyngeal squamous cell carcinoma (OPSCC), toll-like receptors (TLR) 5 and 7 associate with the tumor's human papilloma virus (HPV) status (Jouhi et al., 2017). TLR 2, on the other hand, has been linked to head and neck squamous cell carcinoma (HNSCC), and to oral carcinogenesis (Farnebo et al., 2015; Binder Gallimidi et al., 2015). Here we investigated the presence of TLR 2 and 4 in HPV-positive and HPV-negative OPSCC, and their relationship to opportunistic oral pathogen Treponema denticola chymotrypsin-like protease (Td-CTLP) immunoexpression, clinical parameters, and patient outcome. Materials and methods: Clinicopathological data of 198 unselected consecutive OPSCC patients came from hospital registries. Immunoexpression of TLRs 2 and 4 we evaluated by immunohistochemistry, and earlier in this patient series we studied immunoexpression of Td-CTLP and HPV DNA, HPV mRNA, and p16 status. Results: Immunoexpression of both TLRs 2 and 4 showed a significant association with HPV-status. Strong expression was associated with HPV-positivity and mild expression with HPV-negativity. Patients with strong TLR 2 immunoexpression in the HPV negative subgroup had significantly poorer 5-year DSS (58%) than did patients with mild TLR 2 expression (77%), and strong TLR 2 immunoexpression remained as an independent factor linked to increased disease mortality in the multivariable setting (P = 0.019). No association existed between TLR 2 or 4 and Td-CTLP expression. Conclusion: Our results support the role of TLR 2 receptor as a possible target for development of therapeutics as earlier proposed (Farnebo et al., 2015). The involvement of Td and other oral pathogens in carcinogenesis of OPSCC, remains open and calls for further study.
  • Petain, Sami; Kasnak, Gokhan; Firatli, Erhan; Tervahartiala, Taina; Gürsoy, Ulvi K.; Sorsa, Timo (2021)
    Background and Aims: Chymotrypsin-like-proteinase of Treponema denticola (Td-CTLP) can stimulate the protein expression and activation of matrix metalloproteinase (MMP)-8 (or collagenase-2), a potent tissue destructive enzyme from gingival cells in vitro. The aims of this study were 1) to demonstrate the proMMP-8 (or latent MMP-8) activation by Td-CTLP in vitro and 2) to detect Td-CTLP and MMP-8 protein levels in the tissue samples of peri-implantitis and periodontitis patients. Materials and Methods: proMMP-8 activation by Td-CTLP was analyzed by immunoblots. Tissue specimens were collected from 38 systemically healthy and non-smoking patients; 14 of whom had moderate to severe periodontitis, 10 of whom were suffering from peri-implantitis, and finally 14 of whom showed no sign of periodontal inflammation nor radiological bone decay (control group). The immune-expression levels of MMP-8 and Td-CTLP in the epithelium and the connective tissue were analyzed immunohistochemically. A pixel color-intensity analyze was performed with ImageJ software (version 1.46c; Rasband WS, National Institutes of Health, Bethesda, MD, USA) to obtain a comparable numeral score for each patient's epithelium and connective tissue MMP-8 and Td-CTLP enzyme level. Results: Td-CTLP activated proMMP-8 in vitro by converting the 70 75 kDa proMMP-8 to 65 kDa active MMP-8. Also, lower molecular size 25 50 kDa parts of MMP-8 were formed. There was no statistically significant difference between the study groups in terms of their MMP-8 and Td-CTLP levels in the epithelium or in the connective tissue. Conclusion: Regarding the limits of this study, it can thus be said that the Td-CTLP enzyme can activate the host proMMP-8 enzyme. Tissue protein levels of MMP-8 and Td-CTLP do not seem to be changed in peri-implantitis and in periodontitis.
  • Kylmä, Anna Kaisa; Jouhi, Lauri; Listyarifah, Dyah; Mohamed, Hesham; Mäkitie, Antti; Remes, Satu Maria; Haglund, Caj; Atula, Timo; Nieminen, Mikko; Sorsa, Timo; Hagström, Jaana (Helsingin yliopisto, 2018)
    Background: An opportunistic oral pathogen, Treponema denticola (Td), has been linked to orodigestive carcinogenesis, but its role in oropharyngeal squamous cell carcinoma (OPSCC) has remained open. We evaluated the presence of Td chymotrypsin-like protease (Td-CTLP) in a series of 201 unselected consecutive OPSCC patients, and the relation of the Td-CTLP to human papillomavirus (HPV) status, to expression of toll-like receptors (TLR) 5, 7, and 9, and to clinical parameters and patient outcome. Methods: Clinicopathological data came from hospital registries. The expression of cell-surface-bound Td-CTLP was evaluated by immunohistochemistry. Immunoexpression of TLRs 5, 7, and 9, and HPV status we studied earlier in this patient series. Results: We detected Td-CTLP in 81% of the OPSCC, and especially in HPV-negative tumors (48% of all OPSCCs). Among the HPV-positive tumors (52% of all OPSCCs), low Td-CTLP expression associated with low TLR 5 and high TLR 7 expression. Among those HPV-negative, higher TLR 5 and lower TLR 7 expression associated with high Td-CTLP expression. Strong Td-CTLP expression associated with poor disease-specific survival, but no similar association among HPV-positive and HPV-negative subgroups emerged. Conclusion: Td-CTLP was highly expressed in OPSCC and was associated with the HPV status of tumor tissue.
  • Nieminen, Mikko T.; Listyarifah, Dyah; Hagström, Jaana; Haglund, Caj; Grenier, Daniel; Nordstrom, Dan; Uitto, Veli-Jukka; Hernandez, Marcela; Yucel-Lindberg, Tulay; Tervahartiala, Taina; Ainola, Mari; Sorsa, Timo (2018)
    Background: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. Methods: The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS-PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. Results: Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and alpha-1-antichymotrypsin, as well as complement C1q. Conclusions: Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis.