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Onyedibe KI, Elmanfi S, Aryal UK, et al. Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP. J Oral Microbiol. 2021;14(1):2003617doi: 10.1080/20002297.2021.2003617.
Onyedibe, K. I., Elmanfi, S., Aryal, U. K., Könönen, E., Gürsoy, U. K., & Sintim, H. O. (2022). Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP. Journal of oral microbiology, 14(1), 2003617. https://doi.org/10.1080/20002297.2021.2003617
Onyedibe, Kenneth I, et al. "Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP." Journal of oral microbiology vol. 14,1 (2022): 2003617. doi: https://doi.org/10.1080/20002297.2021.2003617
Onyedibe KI, Elmanfi S, Aryal UK, Könönen E, Gürsoy UK, Sintim HO. Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP. J Oral Microbiol. 2021 Dec 29;14(1):2003617. doi: 10.1080/20002297.2021.2003617. eCollection 2022. PMID: 34992733; PMCID: PMC8725719.
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J Oral Microbiol. 2021 Dec 29;14(1):2003617. doi: 10.1080/20002297.2021.2003617. eCollection 2022.

Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP.

Journal of oral microbiology

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

Affiliations

  1. Department of Chemistry, Purdue University, West Lafayette, USA.
  2. Immunology and Infectious Disease, Purdue Institute for Drug Discovery and Purdue Institute of Inflammation, Purdue University, West Lafayette, USA.
  3. Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.
  4. Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, USA.
  5. Department of Comparative Pathobiology, Purdue University, West Lafayette, USA.

PMID: 34992733 PMCID: PMC8725719 DOI: 10.1080/20002297.2021.2003617

Abstract

BACKGROUND: Constant exposure of human gingival fibroblasts (HGFs) to oral pathogens trigger selective immune responses. Recently, the activation of immune response to cyclic dinucleotides (CDNs) via STING has come to the forefront. Reports show that other proteins outside the STING-TBK1-IRF3 axis respond to CDNs but a global view of impacted proteome in diverse cells is lacking. HGFs are constantly exposed to bacterial-derived cyclic-di-adenosine monophosphate (c-di-AMP) and cyclic-di-guanosine monophosphate (c-di-GMP).

AIM: To understand the response of HGFs to bacterial-derived CDNs, we carried out a global proteomics analysis of HGFs treated with c-di-AMP or c-di-GMP.

METHODS: The expression levels of several proteins modulated by CDNs were examined.

RESULTS: Interferon signaling proteins such as Ubiquitin-like protein ISG15 (ISG15), Interferon-induced GTP-binding protein Mx1 (MX1), Interferon-induced protein with tetratricopeptide repeats (IFIT) 1 (IFIT1), and (IFIT3) were significantly upregulated. Interestingly, other pathways not fully characterized to be regulated by CDNs, such as necroptosis signaling, iron homeostasis signaling, protein ubiquitination, EIF2 signaling, sumoylation and nucleotide excision repair pathways were also modulated by the bacterial-derived CDNs.

CONCLUSION: This study has added to the increasing appreciation that beyond the regulation of cytokine production via STING, cyclic dinucleotides also broadly affect many critical processes in human cells.

© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords: Cyclic dinucleotide; fibroblasts; proteomics

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

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