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




Elmanfi, Samira; Onyedibe, Kenneth I.; Aryal, Uma K.; Könönen, Eija; Sintim, Herman O.; Gürsoy, Ulvi Kahraman

PublisherTAYLOR & FRANCIS LTD

ABINGDON

2025

Journal of Oral Microbiology

JOURNAL OF ORAL MICROBIOLOGY

J ORAL MICROBIOL

2431453

17

1

15

2000-2297

DOIhttps://doi.org/10.1080/20002297.2024.2431453

https://www.tandfonline.com/doi/full/10.1080/20002297.2024.2431453

https://research.utu.fi/converis/portal/detail/Publication/477903469



Background Bacterial cyclic dinucleotides (CDNs), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) upregulate interferon signaling proteins of human gingival fibroblasts (HGFs). However, the simultaneous effect of bacterial CDNs and lipopolysaccharides (LPS) on the HGF proteome is unknown.

Aim The aim was to apply an unbiased proteomics approach to evaluate how simultaneous exposure to CDNs and Porphyromonas gingivalis (Pg) LPS affect the global proteome of HGFs.

Methods The proteomic responses of HGFs were examined under three different treatment conditions (c-di-AMP+Pg LPS, c-di-GMP+Pg LPS, and Pg LPS alone) by label-free quantitative mass spectrometry analysis.

Results Simultaneous exposure to CDNs and Pg LPS significantly upregulated innate immunity-related and interferon signaling-related proteins, such as ubiquitin-like protein ISG15 (ISG15), deoxynucleoside triphosphate triphosphohydrolase (SAMHD1), interferon regulatory factor 9 (IRF-9), interferon-induced GTP-binding protein Mx (MX)1, and MX2. Interferon signaling pathway was the most significantly regulated canonical pathway in both CDN treatment groups.

Conclusion Simultaneous exposure to CDNs and Pg LPS stimulates the periodontal immune response by activating the anti-microbial cellular responses of HGFs with some notable differences from individual exposures.


We thank Purdue Drug Discovery endowment and NSF (grant no. 2004102, HOS), Finnish Doctoral Programme in Oral Sciences (FINDOS-Turku) (SE), and Minerva Foundation (SE) for funding.


Last updated on 2025-23-04 at 10:17