Beta-defensin 1

While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest a complex role for hBD-1 in the host defense against viral infections, as evidenced by its expression in cells involved in viral defense, and its gene regulation in response to viral challenge. This regulation is observed both in vitro and in vivo in humans, as well as with the murine homolog, mBD-1. While numerous reviews have summarized the existing literature on β-defensin gene expression and activity, here we provide a focused review of relevant studies on the virus-mediated regulation of hBD-1 and how this regulation can provide a crucial aspect of the innate immune defense against viral infection.

Objectives: The purpose of this meta-analysis was to reveal a potential association of the four functional polymorphisms in human Beta-defensin 1 (DEFB1) gene: rs1047031(c*5G > A) at 3'UTR and rs11362 (-20 G > A), rs1800972(-44 C > G), and rs1799946 (-52 G > A) at 5'UTR with the risk of common oral cavity pathologies that included periodontitis, caries, lichen planus, and recurrent aphthous stomatitis. Methods: The relevant studies were obtained by the two researchers from PubMed, Scopus, and Web of Science up to April 29, 2020. The manual search of the reference lists was also performed. Studies on DEFB1 gene polymorphisms and oral cavity disorders, using the case-control genetic association analysis approach, and published as full texts in English were included. To assess the association strength, odds ratios (ORs) with their 95% confidence intervals (CIs) were extracted. Results: Thirteen publications met the inclusion criteria and were incorporated in this meta-analysis. Statistically significant values of the association tests were found only for the rs1047031 polymorphism. Allele distribution in the rs1047031 polymorphism was significantly associated with susceptibility to oral cavity pathologies (adjusted P value = 0.003). The rare variant allele carriers had a significantly higher risk for oral disasters under recessive (CC vs CT + TT), and CC vs CT models. No significant correlations between rs11362, rs1800972, and rs1799946 and the risk of oral pathologies were revealed. Conclusions: Significant association between rs1047031 polymorphism and risk of oral pathologies has been found, and therefore, we suggest to include this polymorphism in future research concerning the genetic background of the oral cavity diseases.

Human β-defensin 1 (hBD-1) is a multifaceted antimicrobial peptide being a tumour suppressor and, depending on call of duty, capable of inducing self-nets and neutrophil extracellular traps (NETs) to capture and/or kill bacteria, participates in inflammatory responses in chronic diseases including hBD-3 upregulation and also capable of up/downregulation in the presence of certain species of Lactobacillus sp. Thus, is regulated by host microbiota. Alleles, genotypes and/or altered gene expression of its coding gene, DEFB1, have been associated with several human diseases/conditions ranging from metabolic/chronic (e.g. cancer), infectious (e.g. tuberculosis, HIV/AIDS), inflammatory (gastrointestinal diseases), male infertility and more recently, neurologic (e.g. depression and Alzheimer) and autoimmune diseases (e.g. vitiligo and systemic lupus erythematosus). The present update focuses on novel DEFB1/hBD-1 properties and biomarker features, its biological function and the pharmaceutical potential uses of antimicrobial peptide elicitors (APEs) or the engineered peptide in the treatment of hBD-1-related human diseases.