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.
Dias
Irundika H K
IH
School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, United Kingdom.
Marshall
Lindsay
L
Lambert
Peter A
PA
Chapple
Iain L C
IL
Matthews
John B
JB
Griffiths
Helen R
HR
D018829:Adhesins, Bacterial / Q000494:pharmacology*; D002633:Chemotaxis / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D015870:Gene Expression; D000080867:Gingipain Cysteine Endopeptidases; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology*
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D016209:Interleukin-8; D003546:Cysteine Endopeptidases