Citrullination and proteolytic processing of chemokines by Porphyromonas gingivalis
| Autor: | Erik Martens, Eva Moelants, Gitte Loozen, Paul Proost, Jo Van Damme, Ghislain Opdenakker, Jan Potempa, Wim Teughels, Anneleen Mortier, Danuta Mizgalska, B. Szmigielski |
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| Přispěvatelé: | Clinical Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Hydrolases/metabolism
musculoskeletal diseases Chemokine Proteases Hydrolases Proteolysis Immunology Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Citrulline CXCL10 Interleukin 8 Porphyromonas gingivalis Cells Cultured 030304 developmental biology Chemokine CCL3 0303 health sciences Citrulline/metabolism Cellular Microbiology: Pathogen-Host Cell Molecular Interactions medicine.diagnostic_test biology Chemokine CXCL10/metabolism Interleukin-8 Porphyromonas gingivalis/drug effects Citrullination biology.organism_classification Chemokine CXCL10 Infectious Diseases chemistry Biochemistry Interleukin-8/metabolism biology.protein Protein-Arginine Deiminases Parasitology Chemokine CCL3/metabolism 030215 immunology |
| Zdroj: | Infection and Immunity |
| Popis: | The outgrowth of Porphyromonas gingivalis within the inflammatory subgingival plaque is associated with periodontitis characterized by periodontal tissue destruction, loss of alveolar bone, periodontal pocket formation, and eventually, tooth loss. Potential virulence factors of P. gingivalis are peptidylarginine deiminase (PPAD), an enzyme modifying free or peptide-bound arginine to citrulline, and the bacterial proteases referred to as gingipains (Rgp and Kgp). Chemokines attract leukocytes during inflammation. However, posttranslational modification (PTM) of chemokines by proteases or human peptidylarginine deiminases may alter their biological activities. Since chemokine processing may be important in microbial defense mechanisms, we investigated whether PTM of chemokines by P. gingivalis enzymes occurs. Upon incubation of interleukin-8 (IL-8; CXCL8) with PPAD, only minor enzymatic citrullination was detected. In contrast, Rgp rapidly cleaved CXCL8 in vitro . Subsequently, different P. gingivalis strains were incubated with the chemokine CXCL8 or CXCL10 and their PTMs were investigated. No significant CXCL8 citrullination was detected for the tested strains. Interestingly, although considerable differences in the efficiency of CXCL8 degradation were observed with full cultures of various strains, similar rates of chemokine proteolysis were exerted by cell-free culture supernatants. Sequencing of CXCL8 incubated with supernatant or bacteria showed that CXCL8 is processed into its more potent forms consisting of amino acids 6 to 77 and amino acids 9 to 77 (the 6-77 and 9-77 forms, respectively). In contrast, CXCL10 was entirely and rapidly degraded by P. gingivalis , with no transient chemokine forms being observed. In conclusion, this study demonstrates PTM of CXCL8 and CXCL10 by gingipains of P. gingivalis and that strain differences may particularly affect the activity of these bacterial membrane-associated proteases. |
| Databáze: | OpenAIRE |
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