Regulation of Gingival Epithelial Cytokine Response by Bacterial Cyclic Dinucleotides

Overview

Journal J Oral Microbiol

Specialty Dentistry

Date 2019 Jan 2

PMID 30598733

Citations 18

Authors

Samira Elmanfi

Jie Zhou

Herman O Sintim

Eija Kononen

Mervi Gursoy

Ulvi Kahraman Gursoy

Affiliations

Soon will be listed here.

Abstract

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 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 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.

Citing Articles

Activation of cellular responses by cyclic dinucleotides and lipopolysaccharide: a proteomic study on gingival fibroblasts.

Elmanfi S, Onyedibe K, Aryal U, Kononen E, Sintim H, Gursoy U J Oral Microbiol. 2024; 17(1):2431453.

PMID: 39669221 PMC: 11632945. DOI: 10.1080/20002297.2024.2431453.

Therapeutic potential of farnesoid X receptor agonists for modulating inflammation and periodontal regeneration.

Huang J, Zhang H, Fan X, Wang Y Clin Oral Investig. 2024; 29(1):10.

PMID: 39661179 DOI: 10.1007/s00784-024-06087-2.

Cyclic-di-GMP induces inflammation and acute lung injury through direct binding to MD2.

Qian C, Zhu W, Wang J, Wang Z, Tang W, Liu X Clin Transl Med. 2024; 14(8):e1744.

PMID: 39166890 PMC: 11337466. DOI: 10.1002/ctm2.1744.

Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.

Moylan A, Patel D, OBrien C, Schuler E, Hinson A, Marconi R Mol Oral Microbiol. 2024; 39(5):354-367.

PMID: 38436552 PMC: 11368658. DOI: 10.1111/omi.12458.

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

Yu H, Wang P, Lu H, Guan J, Yao F, Zhang T BMC Oral Health. 2023; 23(1):422.

PMID: 37365568 PMC: 10294445. DOI: 10.1186/s12903-023-03040-9.

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