Regulation of hBD-2, hBD-3, hCAP18/LL37, and Proinflammatory Cytokine Secretion by Human Milk Oligosaccharides in an Organotypic Oral Mucosal Model

Gürsoy, Ulvi Kahraman; Salli, Krista; Söderling, Eva; Gürsoy, Mervi; Hirvonen, Johanna; Ouwehand, Arthur C.

doi:10.3390/pathogens10060739

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…Only two years after the discovery of the discussed molecule, it was shown that it is an important defense component in the oral cavity—hBD-2 is secreted by epithelial cells of the gingival mucosa, which is confirmed both by the expression of mRNA for hBD-2 in these cells and the presence of its product in saliva [ 18 ]. It has been shown that the increase of hBD-2 production in an oral mucosal culture model may be a result of an action of human milk oligosaccharides [ 19 ], which may be important in improving immunity in infants. Interestingly, studies involving children aged from 3 to 16 showed that the levels of both hBD-1 and hBD-2 in saliva increased with age, which concurs with the maturation of the immune system [ 20 ].…”

Section: Hbd-2 and Oral Cavity Epitheliummentioning

confidence: 99%

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cieślik

Bagińska

Górski

et al. 2021

Cells

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Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.

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Section: Hbd-2 and Oral Cavity Epitheliummentioning

confidence: 99%

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cieślik

Bagińska

Górski

et al. 2021

Cells

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“…This study is focused on mono- and disaccharides. The role of dietary oligosaccharides and polysaccharides in regulating HDP gene expression is largely unknown, except that two human milk oligosaccharides were recently found to increase human β-defensin 2 protein synthesis, but not other HDPs or inflammatory cytokines ( Gursoy et al, 2021 ). It will be interesting to explore possible HDP-inducing and other immunomodulatory roles of commonly used dietary oligosaccharides and polysaccharides such as fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides, mannan-oligosaccharides, and inulin, all of which are being actively explored as prebiotics to manage the gut microbiome, gut health, and diseases ( Zhu et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Induction of Chicken Antimicrobial Host Defense Peptide Gene Expression by Butyrate and Sugars

et al. 2021

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Antimicrobial resistance is a major concern to public health demanding effective alternative strategies to disease control and prevention. Modulation of endogenous host defense peptide (HDP) synthesis has emerged as a promising antibiotic alternative approach. This study investigated a potential synergy between sugars and butyrate in inducing HDP gene expression in chickens. Our results revealed that sugars differentially regulated HDP expression in both gene- and sugar-specific manners in chicken HD11 macrophage cells. Among eight mono- and disaccharides tested, all were potent inducers of avian β-defensin 9 (AvBD9) gene (p<0.05), but only galactose, trehalose, and lactose obviously upregulated cathelicidin-B1 (CATHB1) gene expression. The expression of AvBD14 gene, on the other hand, was minimally influenced by sugars. Moreover, all sugars exhibited a strong synergy with butyrate in enhancing AvBD9 expression, while only galactose, trehalose, and lactose were synergistic with butyrate in CATHB1 induction. No synergy in AvBD14 induction was observed between sugars and butyrate. Although lactose augmented the expression of nearly all HDP genes, its synergy with butyrate was only seen with several, but not all, HDP genes. Mucin-2 gene was also synergistically induced by a combination of lactose and butyrate. Furthermore, lactose synergized with butyrate to induce AvBD9 expression in chicken jejunal explants (p<0.05). Mechanistically, hyper-acetylation of histones was observed in response to both butyrate and lactose, relative to individual compounds. Mitogen-activated protein kinase, NF-κB, and cyclic adenosine monophosphate signaling pathways were also found to be involved in butyrate- and lactose-mediated synergy in AvBD9 induction. Collectively, a combination of butyrate and a sugar with both HDP-inducing and barrier protective activities holds the promise to be developed as an alternative to antibiotics for disease control and prevention.

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“…Cellular responses of the organotypic oral mucosal model were stimulated as described previously. 22 The model was activated with P. gingivalis (3×10 6 CFU), F. nucleatum (3×10 6 CFU), P. gingivalis LPS (10 ng), and IL‐1β (150 pg) using a nitrocellulose filter as a scaffold. An organotypic model with only the membrane filter formed the control group.…”

Section: Methodsmentioning

confidence: 99%

Regulation of gingival keratinocyte monocyte chemoattractant protein‐1‐induced protein (MCPIP)‐1 and mucosa‐associated lymphoid tissue lymphoma translocation protein (MALT)‐1 expressions by periodontal bacteria, lipopolysaccharide, and interleukin‐1β

Firatli

Fıratlı

Loimaranta

et al. 2022

Journal of Periodontology

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Background:The aim of this study was to evaluate oral bacteria-and interleukin (IL)-1β-induced protein and mRNA expression profiles of monocyte chemoattractant protein-1-induced protein (MCPIP)-1 and mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 in human gingival keratinocyte monolayers and organotypic oral mucosal models. Methods: Human gingival keratinocyte (HMK) monolayers were incubated with Porphyromonas gingivalis, Fusobacterium nucleatum, P. gingivalis lipopolysaccharide (LPS) and IL-1β. The protein levels of MCPIP-1 and MALT-1 were examined by immunoblots and mRNA levels by qPCR. MCPIP-1 and MALT-1 protein expression levels were also analyzed immunohistochemically using an organotypic oral mucosal model. One-way analysis of variance followed by Tukey correction was used in statistical analyses. Results: In keratinocyte monolayers, MCPIP-1 protein expression was suppressed by F. nucleatum and MALT-1 protein expression was suppressed by F. nucleatum, P. gingivalis LPS and IL-1β. P. gingivalis seemed to degrade MCPIP-1 and MALT-1 at all tested time points and degradation was inhibited when P. gingivalis was heat-killed. MCPIP-1 mRNA levels were increased by P. gingivalis, F. nucleatum, and IL-1β, however, no changes were observed in MALT-1 mRNA levels. Conclusion: Gingival keratinocyte MCPIP-1 and MALT-1 mRNA and protein expression responses are regulated by infection and inflammatory mediators. These findings suggest that periodontitis-associated bacteria-inducedThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Regulation of hBD-2, hBD-3, hCAP18/LL37, and Proinflammatory Cytokine Secretion by Human Milk Oligosaccharides in an Organotypic Oral Mucosal Model

Cited by 11 publications

References 28 publications

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Synergistic Induction of Chicken Antimicrobial Host Defense Peptide Gene Expression by Butyrate and Sugars

Regulation of gingival keratinocyte monocyte chemoattractant protein‐1‐induced protein (MCPIP)‐1 and mucosa‐associated lymphoid tissue lymphoma translocation protein (MALT)‐1 expressions by periodontal bacteria, lipopolysaccharide, and interleukin‐1β

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