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Porphyromonas gingivalis Peptidyl Arginine Deiminase: A Unique Bacterial PAD with Implications for Periodontal Disease and Rheumatoid Arthritis

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Protein Deimination in Human Health and Disease

Abstract

Recently, peptidyl arginine deiminase from Porphyromonas gingivalis (PPAD) has become a subject of an intense research. Despite catalyzing the reaction of citrullination (deimination) and being a member of the guanidino-group modifying superfamily of enzymes, PPAD and the mammalian peptidyl arginine deiminases (PAD/PADI) are phylogenetically unrelated proteins. The citrullination of host and bacterial proteins by PPAD has been implicated in the pathogenesis of periodontitis (PD) and postulated as the link between PD and rheumatoid arthritis (RA). In this chapter, we discuss the role of protein citrullination by PPAD in the pathogenesis of PD and RA.

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Abbreviations

ACPA:

Anti-citrullinated protein antibodies

ADI:

Arginine deiminase

AgDI:

Agmatine deiminase

APD:

Aggressive periodontitis

AST:

Arginine succinyltransferase

AT:

Antithrombin

CD:

Catalytic domain

CEP-1:

Citrullinated enolase peptide-1

CK:

Cytokeratin

CNS:

Central nervous system

COX-2:

Cyclooxygenase-2

CTD:

C-terminal domain

CXCL:

Chemokine

DDAH:

N ω,N ω-dimethylarginine dimethylaminohydrolase

EGF:

Epidermal growth factor

ER:

Estrogen receptor

GATM:

l-arginine-glycine amidinotransferase

GCF:

Gingival crevicular fluid

GFAP:

Glial fibrillary acidic protein

GMEs:

Guanidino-group modifying superfamily of enzymes

HEL:

Hen egg lysozyme

HLA:

Human leukocyte antigen

IgLF:

Immunoglobulin-like fold domain

IL:

Interleukin

KB:

Oral epithelial cell line

LPS:

Lipopolysaccharide

MBP:

Myelin basic protein

MHC:

Major histocompatibility complex

mPGES-1:

Microsomal prostaglandin E synthase-1

MS:

Multiple sclerosis

NET:

Neutrophil extracellular trap

NHANES:

National Health and Nutrition Examination Survey

NSAIDs:

Nonsteroidal anti-inflammatory drugs

NtSP:

N-terminal signal peptide

OMVs:

Outer membrane vesicles

OR:

Odds ratio

P. gingivalis :

Porphyromonas gingivalis

PAD/PADI:

Mammalian peptidyl arginine deiminase

PARs:

Protease-activated receptors

PD:

Periodontitis

PGE2:

Prostaglandin E2

PHGF:

Primary human gingival fibroblasts

PorSS:

Por secretion system of P. gingivalis

PorU:

Sortase

PPAD:

Peptidyl arginine deiminase from P. gingivalis

PTPN22:

Protein-tyrosine phosphatase, non-receptor type 22

RA:

Rheumatoid arthritis

REP-1:

Arginine control peptide

Rgps:

Cysteine proteases (gingipains) from P. gingivalis

SLPI:

Secretory leukocyte protease inhibitor

TERT-2:

Immortalized human oral keratinocytes

TNFα:

Tumor necrosis factor α

TR:

Thyroid receptor

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Acknowledgments

Many thanks to the National Science Centre of Poland (2012/07/B/NZ6/03524 to K.G.) for providing funding to many of the experiments reviewed in this chapter.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Krakow, Poland

    Katarzyna Gawron, Grzegorz Bereta & Jan Potempa

  2. Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

    Anna Montgomery & Patrick Venables

  3. Department of Periodontology and Oral Medicine, Jagiellonian University, Medical College, Krakow, Poland

    Katarzyna Łazarz-Bartyzel & Maria Chomyszyn-Gajewska

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  1. Katarzyna Gawron
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  4. Grzegorz Bereta
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Correspondence to Katarzyna Gawron .

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  1. Department of Neurology, University of Alabama at Birmingham and The Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA

    Anthony P. Nicholas

  2. Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA

    Sanjoy K. Bhattacharya

  3. Department of Biochemistry and Molecular Pharmacology, UMASS Medical School, Worcester, Massachusetts, USA

    Paul R. Thompson

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Gawron, K. et al. (2017). Porphyromonas gingivalis Peptidyl Arginine Deiminase: A Unique Bacterial PAD with Implications for Periodontal Disease and Rheumatoid Arthritis. In: Nicholas, A., Bhattacharya, S., Thompson, P. (eds) Protein Deimination in Human Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-58244-3_7

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