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

Abstract

<p><b>Background</b> 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.<br></p><p><b>Aim</b> 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.<br></p><p><b>Methods</b> 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.<br></p><p><b>Results </b>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.<br></p><p><b>Conclusion </b>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.<br></p>