Antimicrobial Activity of Host-Derived Lipids.

Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective.

Computational Models Accurately Predict Multi-Cell Biomarker Profiles in Inflammation and Cancer.

Individual computational models of single myeloid, lymphoid, epithelial, and cancer cells were created and combined into multi-cell computational models and used to predict the collective chemokine, cytokine, and cellular biomarker profiles often seen in inflamed or cancerous tissues. Predicted chemokine and cytokine output profiles from multi-cell computational models of gingival epithelial keratinocytes (GE KER), dendritic cells (DC), and helper T lymphocytes (HTL) exposed to lipopolysaccharide (LPS) or synthetic triacylated lipopeptide (Pam3CSK4) as well as multi-cell computational models of multiple myeloma (MM) and DC were validated using the observed chemokine and cytokine responses from the same cell type combinations grown in laboratory multi-cell cultures with accuracy. Predicted and observed chemokine and cytokine responses of GE KER + DC + HTL exposed to LPS and Pam3CSK4 matched 75% (15/20, p = 0.

Dataset on the chemokine and cytokine responses of multi-cell cultures treated with hemagglutinin B.

Chemokines and cytokines produced in gingival tissues exposed to microorganisms and microbial products in dental plaque lead to local inflammation and tissue damage seen in periodontal disease. Bates et al. 2018 [1] reported that hemagglutinin B (HagB)-induced matrix metalloproteinase (MMP) responses of single cell cultures containing dendritic cells, gingival epithelial (GE) keratinocytes, or T cells were significantly different from the MMP responses of these same cells grown in multi-cell cultures.

Matrix Metalloproteinase Response of Dendritic Cell, Gingival Epithelial Keratinocyte, and T-Cell Transwell Co-Cultures Treated with Hemagglutinin-B.

Matrix metalloproteinases (MMPs) are enzymes involved in periodontal tissue destruction. Hemagglutinin B (HagB) from the periodontal pathogen induces an elevated MMP response in dendritic cells, but responses from cultures of single-cell types do not reflect the local tissue environment. The objective of this study was to measure HagB-induced MMP responses in a transwell co-culture system containing dendritic cells, gingival epithelial (GE) keratinocytes, and CD4+ T-cells.

Human beta defensin 3 alters matrix metalloproteinase production in human dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B.

Background: Matrix metalloproteinases (MMPs) are zinc- or calcium-dependent proteinases involved in normal maintenance of extracellular matrix. When elevated, they contribute to the tissue destruction seen in periodontal disease. Recently, we found that human beta defensin 3 (HBD3), a cationic antimicrobial peptide, alters chemokine and proinflammatory cytokine responses in human myeloid dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B (HagB).

Diminished Antimicrobial Peptide and Antifungal Antibiotic Activities against Candida albicans in Denture Adhesive.

The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti- activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.

Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida Species Infections.

Purpose: Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes.

Materials And Methods: The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C.

Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models.

Purpose: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity.

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells.

Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1].

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways.

Unlabelled: Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C(16:1Δ6)) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls.

Cytotoxicity of HBD3 for dendritic cells, normal human epidermal keratinocytes, hTERT keratinocytes, and primary oral gingival epithelial keratinocytes in cell culture conditions.

Human β-defensin 3 (HBD3) is a prominent host defense peptide. In our recent work, we observed that HBD3 modulates pro-inflammatory agonist-induced chemokine and cytokine responses in human myeloid dendritic cells (DCs), often at 20.0 μM concentrations.

Novel biomarkers of periodontitis and/or obesity in saliva-An exploratory analysis.

Objective: Recent studies point to the clinical and research utility of saliva as a valuable diagnostic aid for monitoring periodontal health. The objectives of this study were to detect novel biomarkers attributed to chronic inflammation in saliva and to determine if the levels of these markers correlate with severity of periodontitis and with standard obesity measures in participants in a periodontal maintenance program.

Design: In this cross-sectional assessment of 63 participants, unstimulated whole saliva was collected after recording anthropometric and clinical parameters of obesity and periodontitis, respectively.

Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin.

In the skin, aging is associated with overall epidermal thinning, decreased barrier function, and gradual deterioration of the epidermal immune response. However, the presence and role of cytokines, chemokines, and biologic analytes (CCBAs) in immunosenescence are not known. Here we identified age-related changes in skin properties and CCBAs from stratum corneum of healthy human subjects, providing a means to utilize CCBAs as benchmarks for aging skin health.

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells.

Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections.

Antimicrobial Activity of Chemokine CXCL10 for Dermal and Oral Microorganisms.

CXCL10 (IP-10) is a small 10 kDa chemokine with antimicrobial activity. It is induced by IFN-γ, chemoattracts mononuclear cells, and promotes adhesion of T cells. Recently, we detected CXCL10 on the surface of the skin and in the oral cavity.

A cross-sectional assessment of biomarker levels around implants versus natural teeth in periodontal maintenance patients.

Background: Recent studies point to the clinical utility of using peri-implant sulcular fluid (PISF) as a valuable diagnostic aid for monitoring peri-implant tissue health. The objectives of this study are to determine the levels of key biomarkers in PISF in periodontal maintenance participants and compare them with their corresponding levels in gingival crevicular fluid (GCF) obtained from the same participants.

Methods: PISF and GCF were collected from an implant and a contralateral natural tooth after the clinical examination of 73 participants.

Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses.

Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system.

The roles of cutaneous lipids in host defense.

Lauric acid (C12:0) and sapienic acid (C16:1Δ6) derived from human sebaceous triglycerides are potent antimicrobials found at the human skin surface. Long-chain bases (sphingosine, dihydrosphingosine and 6-hydroxysphingosine) are also potent and broad-acting antimicrobials normally present at the skin surface. These antimicrobials are generated through the action of ceramidases on ceramides from the stratum corneum.

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions.

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P.

Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria.

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria.