Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides

Background: Cyclic dinucleotides (cyclic di-guanosine monophosphate (c-di-GMP) and cyclic di-adenosine monophosphate (c-di-AMP)) and lipopolysaccharides (LPS) are pathogen-associated molecular patterns (PAMPs). Individual impacts of PAMPs on immune system have been evaluated, but simultaneous action...

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Main Authors: Samira Elmanfi, Jie Zhou, Herman O. Sintim, Eija Könönen, Mervi Gürsoy, Ulvi Kahraman Gürsoy
Format: Article
Language:English
Published: Taylor & Francis Group 2019-01-01
Series:Journal of Oral Microbiology
Subjects:
Online Access:http://dx.doi.org/10.1080/20002297.2018.1538927
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author Samira Elmanfi
Jie Zhou
Herman O. Sintim
Eija Könönen
Mervi Gürsoy
Ulvi Kahraman Gürsoy
author_facet Samira Elmanfi
Jie Zhou
Herman O. Sintim
Eija Könönen
Mervi Gürsoy
Ulvi Kahraman Gürsoy
author_sort Samira Elmanfi
collection DOAJ
description Background: Cyclic dinucleotides (cyclic di-guanosine monophosphate (c-di-GMP) and cyclic di-adenosine monophosphate (c-di-AMP)) and lipopolysaccharides (LPS) are pathogen-associated molecular patterns (PAMPs). Individual impacts of PAMPs on immune system have been evaluated, but simultaneous actions of multiple PAMPs have not been studied. Objective: Examination the effects of cyclic dinucleotides and Porphyromonas gingivalis LPS on gingival epithelial cytokine response. Methods: Human gingival keratinocytes (HMK) were incubated with 1, 10, and 100 µM concentrations of c-di-GMP and c-di-AMP, either in the presence or absence of P. gingivalis LPS. Intra- and extracellular levels of interleukin (IL)-1β, IL-8, IL-1Ra, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF), were measured using the Luminex technique. Results: LPS decreased extracellular IL-8 levels, while the presence of c-di-AMP inhibited this effect. Incubating HMK cells with c-di-AMP (alone or with LPS) elevated the extracellular level of MCP-1. Extracellular VEGF level increased when cells were incubated with LPS and c-di-GMP together, or with c-di-AMP alone. LPS and c-di-AMP suppressed intracellular IL-1β levels. The c-di-AMP elevated intracellular levels of IL-1Ra. Conclusion: c-di-AMP and, to a lesser extent, c-di-GMP regulate keratinocyte cytokine response, either as an aggregator or as a suppressor of LPS, depending on the cytokine type.
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spelling doaj.art-fcb302f2d0264251b1081c619765f99f2022-12-21T20:29:33ZengTaylor & Francis GroupJournal of Oral Microbiology2000-22972019-01-0111110.1080/20002297.2018.15389271538927Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotidesSamira Elmanfi0Jie Zhou1Herman O. Sintim2Eija Könönen3Mervi Gürsoy4Ulvi Kahraman Gürsoy5University of TurkuPurdue UniversityPurdue UniversityUniversity of TurkuUniversity of TurkuUniversity of TurkuBackground: Cyclic dinucleotides (cyclic di-guanosine monophosphate (c-di-GMP) and cyclic di-adenosine monophosphate (c-di-AMP)) and lipopolysaccharides (LPS) are pathogen-associated molecular patterns (PAMPs). Individual impacts of PAMPs on immune system have been evaluated, but simultaneous actions of multiple PAMPs have not been studied. Objective: Examination the effects of cyclic dinucleotides and Porphyromonas gingivalis LPS on gingival epithelial cytokine response. Methods: Human gingival keratinocytes (HMK) were incubated with 1, 10, and 100 µM concentrations of c-di-GMP and c-di-AMP, either in the presence or absence of P. gingivalis LPS. Intra- and extracellular levels of interleukin (IL)-1β, IL-8, IL-1Ra, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF), were measured using the Luminex technique. Results: LPS decreased extracellular IL-8 levels, while the presence of c-di-AMP inhibited this effect. Incubating HMK cells with c-di-AMP (alone or with LPS) elevated the extracellular level of MCP-1. Extracellular VEGF level increased when cells were incubated with LPS and c-di-GMP together, or with c-di-AMP alone. LPS and c-di-AMP suppressed intracellular IL-1β levels. The c-di-AMP elevated intracellular levels of IL-1Ra. Conclusion: c-di-AMP and, to a lesser extent, c-di-GMP regulate keratinocyte cytokine response, either as an aggregator or as a suppressor of LPS, depending on the cytokine type.http://dx.doi.org/10.1080/20002297.2018.1538927lipopolysaccharideinflammationperiodontitisinterleukinkeratinocytes
spellingShingle Samira Elmanfi
Jie Zhou
Herman O. Sintim
Eija Könönen
Mervi Gürsoy
Ulvi Kahraman Gürsoy
Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
Journal of Oral Microbiology
lipopolysaccharide
inflammation
periodontitis
interleukin
keratinocytes
title Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
title_full Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
title_fullStr Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
title_full_unstemmed Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
title_short Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
title_sort regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides
topic lipopolysaccharide
inflammation
periodontitis
interleukin
keratinocytes
url http://dx.doi.org/10.1080/20002297.2018.1538927
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