Inactivation of epidermal growth factor by Porphyromonas gingivalis as a potential mechanism for periodontal tissue damage

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  • Krzysztof Pyrc, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Aleksandra Milewska, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Tomasz Kantyka, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Aneta Sroka, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Katarzyna Maresz, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Joanna Koziel, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
  • Ky-Anh Nguyen, Institute of Dental Research, Westmead Centre for Oral Health and Westmead Millennium Institute, Australia
  • Jan Johannes Enghild
  • Anders Dahl Knudsen, Denmark
  • Jan Potempa, Microbiology Department, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Poland
Porphyromonas gingivalis is a Gram-negative bacterium associated with the development of periodontitis. The evolutionary success of this pathogen results directly from the presence of numerous virulence factors, including a peptidylarginine deiminase (PPAD), an enzyme, which converts arginine to citrulline in proteins and peptides. Such posttranslational modification is thought to affect the function of many different signaling molecules. Taking into account the importance of tissue remodeling and repair mechanisms for periodontal homeostasis, which are orchestrated by ligands of the epidermal growth factor receptor (EGFR), we investigated the ability of PPAD to distort cross-talk between the epithelium and the EGF signaling pathway. We found that EGF preincubation with purified recombinant PPAD, or a wild-type strain of P. gingivalis, but not with a PPAD-deficient isogenic-mutant, efficiently hindered the ability of the growth factor to stimulate epidermal cell proliferation and migration. In addition, PPAD abrogated EGFR-EGF interaction-dependent stimulation of expression of Suppressor of Cytokine Signaling 3 (SOCS3) and Interferon Regulatory Factor 1 (IRF-1). Biochemical analysis clearly showed that the PPAD-exerted effects on EGF activities were solely due to deimination of the C-terminal arginine. Interestingly, citrullination of two internal Arg residues with human endogenous peptidylarginine deiminases did not alter EFG function, arguing that the C-terminal arginine is essential for EGF biological activity. Cumulatively, these data suggest that PPAD-activity-abrogating EGF function in gingival pockets may at least partially contribute to tissue damage and delayed healing within P. gingivalis-infected periodontia.
Original languageEnglish
JournalInfection and Immunity
Volume81
Issue1
Pages (from-to)55-64
Number of pages10
ISSN0019-9567
DOIs
Publication statusPublished - Jan 2013

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