The Alterations in CD14 Expression in Periodontitis: A Systematic Review

Abstract

Objective: Cluster of differentiation (CD14) is an important protein involved in activating toll-like receptors by bacterial components. It exists as either a transmembrane or soluble protein, called mCD14 or sCD14, respectively. Several studies show that CD14 regulates the inflammatory response to periodontal pathogens, and its expression is altered in periodontitis, an inflammatory disease of tooth-supporting tissues. It is the intent of this review to investigate the levels of expression of mCD14 and sCD14 in peripheral blood monocytes, saliva, gingival crevicular fluid, and gingival tissue biopsies in periodontitis patients. Methods: PubMed, Scopus, Ovid/Medline, Embase, and the Cochrane Library were consulted for the online literature search. To ensure methodical quality, titles and abstracts were reviewed in accordance to the PRISMA guidelines. Data extraction and evaluation of the full texts were executed in agreement with the GRADE approach. Results: This systematic review shows that mCD14 levels are decreased in peripheral blood monocytes of periodontitis patients in comparison to healthy patients, while sCD14 levels in sera, gingival crevicular fluid (GCF), and biopsies of periodontitis patients have a tendency to be increased in comparison to healthy controls. The evaluation of CD14 in gingival biopsies and periodontal tissues elucidated the fact that interpretation of the data obtained with qPCR, ELISA, and flow cytometry is questionable.

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease

“…Proteins that have low or no expression in saliva or salivary glands were also excluded from the validation list. The final shortlisted hits, namely, peroxiredoxin‐4 (PRX‐IV), legumain, SIL1 nucleotide exchange factor (SIL1), and cellular repressor of E1A‐stimulated genes (CREG1), were chosen based on novelty, 27–41 and the absence of association with other oral diseases 42–47 …”

“…The final shortlisted hits, namely, peroxiredoxin-4 (PRX-IV), legumain, SIL1 nucleotide exchange factor (SIL1), and cellular repressor of E1A-stimulated genes (CREG1), were chosen based on novelty, [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and the absence of association with other oral diseases. [42][43][44][45][46][47] 2.2 | Salivary PRX-IV and legumain are significantly upregulated in HFMD case samples from Singapore Dot blot validation assay was performed using saliva samples from HFMD-diagnosed patients and healthy volunteers in Singapore to assess the sensitivity and specificity of the respective biomarker(s). A total of 28 HFMD cases and 43 healthy saliva samples were used for validation.…”

The Association between Maternal Oral Inflammation and Neutrophil Phenotypes and Poly-Unsaturated Fatty Acids Composition in Human Milk: A Prospective Cohort Study

“…This change in the expression levels might be related to the presence of pathogenic gram-negative anaerobic microorganisms of periodontal diseases in human milk such as Porphyromonas gingivalis [ 48 ]. CD14 biomarker expressed on PMNs acts as a receptor for the LPS of gram-negative bacteria and studies reported higher expression levels of CD14 on oPMNs of patients with periodontitis compared to healthy individuals [ 49 ]. Since the pathogenicity of gram-negative anaerobic bacteria of periodontal diseases lie in its endotoxins including LPS [ 49 ], therefore it can be hypothesized that the higher expression levels of CD14 on hmPMNs of mothers with moderate to severe OIL might be related to the presence of these pathogenic bacteria in their human milk.…”

“…CD14 biomarker expressed on PMNs acts as a receptor for the LPS of gram-negative bacteria and studies reported higher expression levels of CD14 on oPMNs of patients with periodontitis compared to healthy individuals [ 49 ]. Since the pathogenicity of gram-negative anaerobic bacteria of periodontal diseases lie in its endotoxins including LPS [ 49 ], therefore it can be hypothesized that the higher expression levels of CD14 on hmPMNs of mothers with moderate to severe OIL might be related to the presence of these pathogenic bacteria in their human milk. Furthermore, studies have shown that the virulence factors of pathogenic bacteria can interfere with the neutrophils’ bactericidal activities, chemotaxis, and inhibition of neutrophil phagocytosis, where recent studies have shown that the upregulation of CD64 biomarker was inhibited when exposed to pathogenic oral bacteria, as opposed to its upregulation in case of commensal bacteria [ 48 ].…”

Role of CD14+ CD16+ Monocytes in the Pathogenesis of Periodontitis Associated Systemic Diseases

“…These cells may be epithelium, fibroblast and so on. Therefore, it should be recognized that all forms of CD14 function as a receptor for byproducts of bacterial cell wall [32].…”