Blockade of protease-activated receptors on T cells correlates with altered proteolysis of CD27 by gingipains of Porphyromonas gingivalis.
Cysteine proteinases, termed gingipains, of Porphyromonas gingivalis are able to inactivate a broad range of host proteins involved in cellular responses and have been implicated as key virulence factors in the onset and progression of adult periodontitis. In the present study, the high molecular weight Arg-gingipain, RgpA, produced a time- and concentration-dependent hydrolysis of the tumour necrosis factor (TNF)-alpha receptor family member CD27 on resting T cells. As a consequence of CD27 degradation, a reduction in CD27-ligation dependent co-stimulatory CD40L expression was observed. Concomitantly, RgpA activated the protease-activated receptors (PAR)-1, PAR-2 and PAR-4 and induced CD69 and CD25 expression on T cells, thereby demonstrating T cell activation. The Lys-gingipain Kgp demonstrated a low capacity to degrade CD27 but the ability to affect CD27 expression and biological activity was increased when T cells were pretreated with blocking peptide against PAR-2. CD70, the ligand for CD27 induced on activated B cells, was significantly reduced by RgpA treatment and weakly affected by Kgp. These findings suggest that while RgpA can activate T cells through PARs, the parallel action of direct hydrolysis of membrane CD27 as well as CD70 indicates a potential down-regulatory effect through inhibition of CD27/CD70-mediated cell activation in periodontitis.
Yun
L W P
LW
Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, Westmead Hospital, Sydney, New South Wales, Australia. plwyun@yahoo.com
Decarlo
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AA
Hunter
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N
D018829:Adhesins, Bacterial / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D053282:CD27 Ligand / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D045604:Extracellular Fluid / Q000276:immunology; D005557:Formaldehyde / Q000494:pharmacology; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D011108:Polymers / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D044462:Receptors, Proteinase-Activated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044967:Serum; D012995:Solubility; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D000099192:CD69 Antigens
D018829:Adhesins, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053282:CD27 Ligand; D023201:CD40 Ligand; D003546:Cysteine Endopeptidases; D005557:Formaldehyde; D000080867:Gingipain Cysteine Endopeptidases; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D011108:Polymers; D044462:Receptors, Proteinase-Activated; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000099192:CD69 Antigens; C003043:paraform