Activation of Notch-1 in oral epithelial cells by P. gingivalis triggers the expression of the antimicrobial protein PLA2-IIA article

Ahmad Al-Attar, Yelena Alimova, Sreenatha Kirakodu, Anastasia Kozal, Michael John Novak, Arnold J. Stromberg, Luis Orraca, Janis Gonzalez-Martinez, Melween Martinez, Jeffrey L. Ebersole, Octavio A. Gonzalez

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

P. gingivalis (Pg) is an oral pathogen with the ability to induce oral dysbiosis and periodontal disease. Nevertheless, the mechanisms by which mucosal responses to the oral microbiota in the presence of specific pathogens such as Pg could abrogate the host-microbe symbiotic relationship leading to periodontitis remain unclear. Herein, we identified the Notch-1/PLA2-IIA axis as a new molecular pathway through which Pg could be specifically modulating oral epithelial antimicrobial and inflammatory responses. Pg activated Notch-1, and inhibition or silencing of Notch-1 completely abrogated Pg-induced PLA2-IIA in oral epithelial cells (OECs). Activation of Notch-1 and PLA2-IIA production were associated with Pg-produced gingipains. Other oral Gram-positive and Gram-negative species failed to induce similar responses. Pg enhanced OEC antimicrobial activity through PLA2-IIA. Increased Notch-1 activation correlated with higher PLA2-IIA gingival expression and changes in the abundance of specific oral bacteria phyla during periodontal disease. Oral bacterial species exhibited differential antimicrobial susceptibility to PLA2-IIA. These findings support previous evidence suggesting an important role for epithelial Notch-1 activation and PLA2-IIA production during health and disease at mucosal surfaces, and provide new mechanistic information concerning the regulation of epithelial antimicrobial and pro-inflammatory responses modulated by oral pathogenic bacteria associated with periodontal disease.

Original languageEnglish
Pages (from-to)1047-1059
Number of pages13
JournalMucosal Immunology
Volume11
Issue number4
DOIs
StatePublished - Jul 1 2018

Bibliographical note

Funding Information:
We would like to thank Drs. Richard Lamont (University of Louisville), Ann Progulske-Fox (University of Florida) and Sarah D’Orazio (UK) for their generosity in sharing the TIGK cells, Pg mutant strains for gingipains, and Lm strain respectively. We also thank the Genetics Core from University of Kentucky for their support with Nanostring and 16S sequencing experiments. NIH/NIDCR Grant DE024804 and NIH/NIGMS Grant P20GM103538 supported this research.

Publisher Copyright:
© 2018 Society for Mucosal Immunology.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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