Gingipains from Porphyromonas gingivalis increase the chemotactic and respiratory burst-priming properties of the 77-amino-acid interleukin-8 variant


Porphyromonas gingivalis, a gram-negative anaerobe which is implicated in the etiology of active periodontitis, secretes degradative enzymes (gingipains) and sheds proinflammatory mediators (e.g., lipopolysaccharides [LPS]). LPS triggers the secretion of interleukin-8 (IL-8) from immune (72-amino-acid [aa] variant [IL-8(72aa)]) and nonimmune (IL-8(77aa)) cells. IL-8(77aa) has low chemotactic and respiratory burst-inducing activity but is susceptible to cleavage by gingipains. This study shows that both R- and K-gingipain treatments of IL-8(77aa) significantly enhance burst activation by fMLP and chemotactic activity (P < 0.05) but decrease burst activation and chemotactic activity of IL-8(72aa) toward neutrophil-like HL60 cells and primary neutrophils (P < 0.05). Using tandem mass spectrometry, we have demonstrated that R-gingipain cleaves 5- and 11-aa peptides from the N-terminal portion of IL-8(77aa) and the resultant peptides are biologically active, while K-gingipain removes an 8-aa N-terminal peptide yielding a 69-aa isoform of IL-8 that shows enhanced biological activity. During periodontitis, secreted gingipains may differentially affect neutrophil chemotaxis and activation in response to IL-8 according to the cellular source of the chemokine.

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Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
Additional Information: Copyright of American Society for Microbiology
Uncontrolled Keywords: Porphyromonas gingivalis,anaerobe,etiology,active periodontitis,secretes degradative enzymes,gingipains,proinflammatory mediators,lipopolysaccharides,interleukin-8,immune,variant,nonimmune,cells,low chemotactic,respiratory,neutrophils,spectrometry,chemokine,Immunology
Publication ISSN: 1098-5522
Last Modified: 17 May 2024 07:07
Date Deposited: 27 Nov 2012 15:24
Full Text Link: http://iai.asm. ... ourcetype=HWFIG
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2008-01
Authors: Dias, Irundika H.K. (ORCID Profile 0000-0002-6620-8221)
Marshall, Lindsay (ORCID Profile 0000-0001-7281-7974)
Lambert, Peter A. (ORCID Profile 0000-0002-8243-2741)
Chapple, Iain L.C.
Matthews, John B.
Griffiths, Helen R. (ORCID Profile 0000-0002-2666-2147)


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