This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tam, V.
Right arrow Articles by Reynolds, E. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tam, V.
Right arrow Articles by Reynolds, E. C.

 Previous Article  |  Next Article 

Infection and Immunity, April 2009, p. 1451-1458, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01377-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The RgpA-Kgp Proteinase-Adhesin Complexes of Porphyromonas gingivalis Inactivate the Th2 Cytokines Interleukin-4 and Interleukin-5{triangledown}

Vivian Tam,1 Neil M. O'Brien-Simpson,1 Yu-Yen Chen,1 Colin J. Sanderson,2 Beverley Kinnear,2 and Eric C. Reynolds1*

Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia,1 Curtin University School of Biomedical Sciences and the Western Australian Institute of Medical Research, Molecular Immunology Group, Perth, Western Australia, 6000, Australia2

Received 10 November 2008/ Returned for modification 15 December 2008/ Accepted 15 January 2009

The RgpA-Kgp proteinase-adhesin complexes are a primary virulence factor of Porphyromonas gingivalis, a major pathogen in the development of chronic periodontitis. The RgpA-Kgp complexes have been suggested to bias the immune response to a Th2 phenotype in disease by hydrolysis of Th1 cytokines. Here, we show that the RgpA-Kgp complexes hydrolyze and inactivate interleukin-4 (IL-4) and IL-5 under physiologically relevant conditions. Using the IL-4/IL-5-dependent TF1.8 T-cell line, it was found that at equimolar ratios of cytokine to RgpA-Kgp complexes, IL-4 and IL-5 were inactivated in the culture medium. The inactivation of IL-4 and IL-5 was RgpA-Kgp concentration dependent, as at an enzyme-to-cytokine molar ratio of 1:8, the bioactivity of the cytokines was greater than at the higher concentration of RgpA-Kgp of 1:1. Furthermore, inactivation of the cytokines by the RgpA-Kgp complexes was time dependent, as longer preincubation times resulted in lower cytokine activity. IL-5 was found to be slightly more resistant to inactivation than IL-4. Mass spectrometric analyses of IL-4 and IL-5 showed that hydrolysis by RgpA-Kgp complexes was C terminal to Arg and Lys residues of the cytokines. The peptides released indicated that the regions of IL-4 and IL-5 important for bioactivity were being hydrolyzed in the first 15 min of incubation. The ability of the RgpA-Kgp complexes to degrade Th2 cytokines may contribute to immune dysregulation and may play a role in the pathology of chronic periodontitis.

* Corresponding author. Mailing address: Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia. Phone: 61 3 9341 1547. Fax: 61 3 9341 1596. E-mail: e.reynolds{at}unimelb.edu.au

{triangledown} Published ahead of print on 21 January 2009.

Editor: B. A. McCormick

Infection and Immunity, April 2009, p. 1451-1458, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01377-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»