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- Björnfot Holmström, Sofia, et al.
(författare)
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MMP-12 and S100s in saliva reflect different aspects of periodontal inflammation
- 2019
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Ingår i: Cytokine. - : Academic Press. - 1043-4666 .- 1096-0023. ; 113, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinase (MMP)-12, S100A8/A9, and S100A12 are involved in innate immune responses. We addressed whether different aspects of oral health and non-disease-related covariates influence their levels in saliva. 436 participants were clinically examined, completed a health questionnaire, and provided stimulated saliva. Salivary levels of MMP-12, S100A8/A9, and S100A12 were determined by enzyme-linked immunosorbent assays. Lower MMP-12 levels were observed in individuals 40-64years old (yo) compared to < 40yo, and higher S100A8/A9 levels were found in individuals > 64yo compared to 40-64yo. Smokers exhibited lower MMP-12 and S100A12 levels compared to non-smokers. All three proteins were elevated in individuals with bleeding on probing (BOP)>20% compared to those with BOP/= 10% gingival pocket depths (PPD)>/=4mm compared to the ones with shallow pockets < 4mm. The extent of alveolar bone loss or presence of manifest caries did not alter any of the markers. MMP-12, S100A8/A9, and S100A12 levels were higher in participants with high periodontal inflammatory burden. All three proteins correlated positively to BOP, PPD, and to several inflammatory mediators. The explanatory variables for MMP-12 in saliva were age, smoking, presence of any tumor, and percentage of PPD>/=4mm. The determinant of salivary S100A8/A9 was percentage of BOP, while S100A12 levels were associated with percentage of BOP and presence of any tumor. Taken together, MMP-12 and the S100/calgranulin levels in saliva reflect different aspects of periodontal inflammation. Smoking and age should be taken into account in further investigation of these proteins as biomarker candidates of periodontal disease.
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| 2. |
- Lira-Junior, Ronaldo, et al.
(författare)
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S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- S100A12 is a calcium-binding protein of the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. It has been linked to several chronic inflammatory diseases, however its role in the common oral immunopathology periodontitis is largely unknown. Previous in vitro monoculture experiments indicate that S100A12 production decreases during monocyte differentiation stages, while the regulation within tissue is poorly defined. This study evaluated S100A12 expression in monocyte subsets, during monocyte-to-macrophage differentiation and following polarization, both in monoculture and in a tissue context, utilizing a three-dimensional co-culture oral tissue model. Further, we explored the involvement of S100A12 in periodontitis by analyzing its expression in peripheral circulation and gingival tissue, as well as in saliva. We found that S100A12 expression was higher in classical than in non-classical monocytes. S100A12 expression and protein secretion declined significantly during monocyte-to-macrophage differentiation, while polarization of monocyte-derived macrophages had no effect on either. Peripheral monocytes from periodontitis patients had higher S100A12 expression than monocytes from controls, a difference particularly observed in the intermediate and non-classical monocyte subsets. Further, monocytes from periodontitis patients displayed an increased secretion of S100A12 compared with monocytes from controls. In oral tissue cultures, monocyte differentiation resulted in increased S100A12 secretion over time, which further increased after inflammatory stimuli. Likewise, S100A12 expression was higher in gingival tissue from periodontitis patients where monocyte-derived cells exhibited higher expression of S100A12 in comparison to non-periodontitis tissue. In line with our findings, patients with severe periodontitis had significantly higher levels of S100A12 in saliva compared to non-periodontitis patients, and the levels correlated to clinical periodontal parameters. Taken together, S100A12 is predominantly secreted by monocytes rather than by monocyte-derived cells. Moreover, S100A12 is increased in inflamed tissue cultures, potentially as a result of enhanced production by monocyte-derived cells. This study implicates the involvement of S100A12 in periodontitis pathogenesis, as evidenced by increased S100A12 expression in inflamed gingival tissue, which may be due to altered circulatory monocytes in periodontitis.
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| 3. |
- Majster, Mirjam
(författare)
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Gateway to the gut : alterations in saliva in inflammatory bowel disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel disease (IBD), which consists of Crohn’s disease and ulcerative colitis, is a chronic immune-mediated disease thought to result from genetic and environmental interaction which influence the commensal flora to trigger an inappropriate mucosal immune response. IBD primarily affects the intestines but is not restricted to them. Extraintestinal manifestations are frequently observed within the oral cavity. This thesis aimed to investigate different mediators of inflammation within the intestines and oral cavity as a reflection of defective immune responses in IBD. In our first study, we investigated the intestinal localization of macrophage growth factors IL-34 and CSF-1 and their involvement in IBD. IL-34 and CSF-1 demonstrated distinct expression patterns in the human intestine and were significantly elevated in human and experimental IBD. Infiltrating cells of the lamina propria and intestinal epithelial cells expressed IL-34, regulated by TNF-α through the NF-κB pathway. As a result, the newly discovered growth factor IL-34 was proposed as a new modulator of IBD. The remaining part of this thesis investigated the expression of inflammatory proteins in saliva in relation to IBD. The second study aimed to analyze calprotectin, an established fecal marker of IBD, for the first time in saliva of IBD patients. We found that calprotectin was significantly elevated in saliva of IBD patients, particularly in CD and most prominently in newly diagnosed CD patients. This opened up for new hypotheses in the oral-gut connection in IBD and supported the notion that the oral cavity may contain early evidence of intestinal inflammation. In a third study, we compared the profile of 92 known inflammatory proteins in saliva and serum of IBD patients. The salivary and circulatory inflammatory profiles were similar but reflected different aspects of IBD activity. Several serum proteins were significantly altered in IBD patients compared to controls, whereas IL-6 and MMP-10 – proteins involved in the pathogenesis of IBD and its extraintestinal manifestations – were significantly elevated in stimulated saliva of IBD patients, providing additional proof of subclinical inflammatory mimicry of intestinal disease by the oral cavity. In the final study, we confirmed our previous findings related to elevated salivary calprotectin in IBD and showed that the concentrations were not significantly affected by oral disease. Moreover, we investigated potential sources of salivary calprotectin and showed that neutrophils isolated from saliva express calprotectin, demonstrate reduced CD11b expression in IBD patients, but share a similar ability to secrete calprotectin. In conclusion, the work presented in this thesis highlights the aberrant immune responses associated to IBD and provides proof that such mechanisms can be reflected by the oral cavity.
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