Salivary and gingival CXCL8 correlation with periodontal status, periodontal pathogens, and smoking

Frasheri, Iris; Heym, Richard; Ern, Christina; Summer, Burkhard; Hennessen, Till G.; Högg, Christof; Reichl, Franz‐Xaver; Folwaczny, Matthias

doi:10.1111/odi.13994

Cited by 7 publications

(11 citation statements)

References 66 publications

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“…Immunofluorescence analysis detected CXCL8, a core gene in the PPI network, and confirmed that both ZIF-8 and Mino had an effect on the expression of inflammatory factors. Numerous studies have reported significantly increased mRNA and protein levels of CXCL8 in inflammatory gingival tissue sections compared to healthy gingiva . Moreover, CXCL8 levels have shown correlations with clinical indicators of periodontitis, such as bleeding on probing, probing depth, and clinical attachment loss, suggesting an excessive immune response as the primary cause of periodontal tissue destruction .…”

Section: Resultsmentioning

confidence: 99%

ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis

Li,

Xu,

Mao

et al. 2024

ACS Appl. Mater. Interfaces

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Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn 2+ with proantioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn 2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3β/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.

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Section: Resultsmentioning

confidence: 99%

ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis

Li,

Xu,

Mao

et al. 2024

ACS Appl. Mater. Interfaces

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“…CXCL8 is more than an inflammatory cytokine, as it is expressed in healthy periodontal tissues, suggesting its involvement in the permanent need for the periodontium to defend against the microbial burden of the oral cavity [ 10 ]. Moreover, once homeostasis shifts into the pathological stage, CXCL8 becomes a marker of periodontitis [ 8 , 9 , 10 ] and periimplantitis [ 11 ]. The fibroblasts are the primary producers of CXCL8 in periodontitis tissues [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…CXCL8 expression is a double-edged sword: (i) it supports local immunity being constantly expressed at a low level, (ii) or at transient higher levels during wound healing, (iii) however, when chronically expressed at high levels, CXCL8 becomes a key mediator associated with pathological inflammation and overaccentuated neutrophil recruitment and degranulation, overall causing tissue damage [ 7 ]. It is, therefore, not surprising that in healthy periodontal tissues, CXCL8 is regularly expressed to control tissue homeostasis, but CXCL8 is increasingly expressed in the pathological conditions of periodontitis [ 8 , 9 , 10 ] and periimplantitis [ 11 ]. Importantly, evidence suggests that fibroblasts are the primary source of CXCL8 in periodontitis [ 10 ] and periimplantitis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Platelet-Rich Fibrin Increases CXCL8 Expression in Gingival Fibroblasts

Imani,

Panahipour,

dos Santos Sanches

et al. 2024

Biomedicines

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Platelet-rich fibrin (PRF), the coagulated plasma of fractionated blood, is widely used to support tissue regeneration in dentistry, and the underlying cellular and molecular mechanisms are increasingly being understood. Periodontal connective tissues steadily express CXCL8, a chemokine that attracts granulocytes and lymphocytes, supporting homeostatic immunity. Even though PRF is considered to dampen inflammation, it should not be ruled out that PRF increases the expression of CXCL8 in gingival fibroblasts. To test this hypothesis, we conducted a bioassay where gingival fibroblasts were exposed to PRF lysates and the respective serum. We show here that PRF lysates and, to a lesser extent, PRF serum increased the expression of CXCL8 by the gingival fibroblasts, as confirmed by immunoassay. SB203580, the inhibitor of p38 mitogen-activated protein kinase, reduced CXCL8 expression. Consistently, PRF lysates and, to a weaker range, the PRF serum also caused phosphorylation of p38 in gingival fibroblasts. Assuming that PRF is a rich source of growth factors, the TGF-β receptor type I kinase inhibitor SB431542 decreased the PRF-induced expression and translation of CXCL8. The findings suggest that PRF lysates and the respective serum drive CXCL8 expression by activating TGF-β and p38 signaling in gingival fibroblasts.

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“…Saliva is an ideal medium for biomarker discovery due to its non-invasive, safe, and simple collection process, which facilitates repeated sampling with minimal discomfort to the patient (5). Inflammatory mediators, such as Interleukin 6 (IL-6) and Interleukin 8 (IL-8), along with total salivary proteins, are gaining attention as salivary biomarkers because they are closely related to the progression of periodontal disease (2,(6)(7)(8). This interest is based on several studies that have reported elevated levels of these analytes in the saliva of patients with periodontal disease, highlighting their potential usefulness as diagnostic indicators or markers of disease progression (5,9,10).…”

Section: Introductionmentioning

confidence: 99%

“…Interleukin-6 (IL-6) plays a pivotal role in periodontal disease, not only because it is intricately involved in the bone resorption process characteristic of periodontitis but also as a regulator of acute phase proteins in inflammation (9,11). Similarly, Interleukin-8 (IL-8) is crucial for the innate immune response to microorganisms in dental biofilm, facilitating neutrophil recruitment and angiogenesis (6,12). Additionally, the total protein content in saliva is gaining recognition as a promising biomarker.…”

Section: Introductionmentioning

confidence: 99%

Variability of salivary analytes under daily conditions and their implications for periodontitis biomarkers

Rocha,

Orlandini,

Motta

et al. 2024

Front. Dent. Med

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IntroductionRecent studies have identified inflammatory mediators as potential biomarkers for monitoring or diagnosing periodontitis. However, the brief half-life of these mediators, coupled with their variability among different individuals and across different stages of periodontal disease, may limit their reliability as biomarkers.MethodsIn this study, we assessed the concentration profile of salivary biomarkers (IL-6, IL-8, and total protein) through repeated measurements within the same day and across different days in 79 patients exhibiting various states of periodontal health: intact periodontium, stable periodontitis, and active periodontitis. Additionally, we explored how daily variations, such as the interval between toothbrushing and eating, impact the levels of these salivary biomarkers and their diagnostic efficacy for periodontitis activity.ResultsOur results showed high salivary levels of IL-6 and total proteins in periodontitis patients (p < 0.001), with detection ability reflected by an Area Under the Receiver Operating Characteristic Curve (AUC-ROC) ranging between 0.709 and 0.852. Conversely, IL-8 levels were higher in patients with intact periodontium (p < 0.001), with an AUC-ROC for periodontitis detection between 0.671 and 0.815. Daily activities such as toothbrushing and eating influenced the levels of specific analytes, particularly total proteins (p < 0.001), but this did not affect their ability to detect periodontal disease activity. The highest measurement agreement, assessed by Intraclass Correlation Coefficients (ICC), was found for IL-6, with no significant differences in agreement between same-day and different-day measurements.ConclusionsOur study demonstrated consistency in the repeated measurements of salivary analytes, both within the same day and across different days, except for salivary total protein levels. These analytes exhibited variability within a range that did not undermine their effectiveness as biomarkers for periodontal disease.

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Salivary and gingival CXCL8 correlation with periodontal status, periodontal pathogens, and smoking

Cited by 7 publications

References 66 publications

ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis

ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis

Platelet-Rich Fibrin Increases CXCL8 Expression in Gingival Fibroblasts

Variability of salivary analytes under daily conditions and their implications for periodontitis biomarkers

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