Bacterial infections constitute a threat to public health as antibiotics are becoming less effective due to the emergence of antimicrobial resistant strains and biofilm and persister formation. Antimicrobial peptides (AMPs) are considered excellent alternatives to antibiotics; however, they suffer from limitations related to their peptidic nature and possible toxicity. The present review critically evaluates the chemical characteristics and antibacterial effects of lipid and polymeric AMP delivery systems and coatings that offer the promise of enhancing the efficacy of AMPs, reducing their limitations and prolonging their half-life. Unfortunately, the antibacterial activities of these systems and coatings have mainly been evaluated in vitro against planktonic bacteria in less biologically relevant conditions, with only some studies focusing on the antibiofilm activities of the formulated AMPs and on the antibacterial effects in animal models. Further improvements of lipid and polymeric AMP delivery systems and coatings may involve the functionalization of these systems to better target the infections and an analysis of the antibacterial activities in biologically relevant environments. Based on the available data we proposed which polymeric AMP delivery system or coatings could be profitable for the treatment of the different hard-to-treat infections, such as bloodstream infections and catheter- or implant-related infections.
Objective
The objective of the present study was to evaluate the anti‐inflammatory effects of lipoxin A4 (LXA4) for the treatment of periodontitis in an in vitro model.
Methods
Human PDLCs were challenged with Escherichia coli (E. coli) lipopolysaccharide (LPS) to evoke an inflammatory response. This was done either in monoculture or in coculture with THP‐1, a monocytic cell line. Thereafter, cytokine expression was measured by ELISA, with or without LXA4. In addition, the effects of LXA4 were analyzed on the TLR‐MyD88‐NF‐κB (TMN)‐mediated intracellular signal pathway using immunocytochemistry.
Results
In response to LPS, the level of the pro‐inflammatory cytokine tumor necrosis factor alpha increased, whereas the anti‐inflammatory cytokine interleukin‐4 decreased significantly (p < .05). These effects were consistently reversed when LPS‐challenged PDLCs were also treated with LXA4. The results in the coculture system were comparable to the monoculture. Immunohistochemistry and quantitative assessment confirmed the importance of the TMN signal pathway in these processes.
Conclusion
These results corroborate earlier findings that PDLCs play an important role in inflammation. Moreover, LXA4 might offer new approaches for the therapeutic treatment of periodontal disease.
Scaling and root planning is a key element in the mechanical therapy used for the eradication of biofilm, which is the major etiological factor for periodontitis and peri‐implantitis. However, periodontitis is also a host mediated disease, therefore, removal of the biofilm without adjunctive therapy may not achieve the desired clinical outcome due to persistent activation of the innate and adaptive immune cells. Most recently, even the resident cells of the periodontium, including periodontal ligament fibroblasts, have been shown to produce several inflammatory factors in response to bacterial challenge. With increased understanding of the pathophysiology of periodontitis, more research is focusing on opposing excessive inflammation with specialized pro‐resolving mediators (SPMs). This review article covers the major limitations of current standards of care for periodontitis and peri‐implantitis, and it highlights recent advances and prospects of SPMs in the context of tissue reconstruction and regeneration. Here, we focus primarily on the role of SPMs in restoring tissue homeostasis after periodontal infection.
Objectives
The objective of the present study was to investigate the effect of lipoxin-type A4 (LXA4) on bacterial-induced osteoclastogenesis.
Material and methods
Human periodontal ligament cells (PDLCs) in coculture with osteoclast precursors (RAW264.7 cells) were exposed to bacterial stimulation with lipopolysaccharide (LPS) to induce inflammation. After 24 h, cells were treated to 100 ng/ml of LXA4 and 50 ng/ml of forymul peptide receptor 2 (FPR2/ALX) receptor antagonist (Boc-2). After 5 days, osteoclastic resorptive activity was assessed on calcium phosphate (CaP) synthetic bone substitute. Additionally, osteoclastic differentiation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP enzymatic activity assay, and on the expression of osteoclast-specific genes.
Results
We found that stimulation of in the osteoclasts with LPS-stimulated PDLCs induced a significant increase in tartrate-resistant acid phosphatase (TRAP) positive cells, higher resorptive activity, and enhanced expression of specific genes. Meanwhile, LXA4-treatment exhibited strong anti-inflammatory activity, and was able to reverse these inflammatory effects.
Conclusions
We conclude that (1) PDLCs are a potential target for treating bacterial-induced bone resorption in patients with periodontal disease, and (2) LXA4 is a suitable candidate for such therapy.
Clinical relevance
The results prove that lipoxins have a protective role in bacterial-induced periodontal inflammation and alveolar bone resorption, which can be translated into a clinical beneficial alterative treatment.
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