{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:14:42Z","timestamp":1789528482905,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The RgpA-Kgp proteinase-adhesin complexes are a primary virulence factor of<jats:italic>Porphyromonas gingivalis<\/jats:italic>, 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.<\/jats:p>","DOI":"10.1128\/iai.01377-08","type":"journal-article","created":{"date-parts":[[2009,1,24]],"date-time":"2009-01-24T02:41:02Z","timestamp":1232764862000},"page":"1451-1458","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["The RgpA-Kgp Proteinase-Adhesin Complexes of<i>Porphyromonas gingivalis<\/i>Inactivate the Th2 Cytokines Interleukin-4 and Interleukin-5"],"prefix":"10.1128","volume":"77","author":[{"given":"Vivian","family":"Tam","sequence":"first","affiliation":[{"name":"Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil M.","family":"O'Brien-Simpson","sequence":"additional","affiliation":[{"name":"Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yen","family":"Chen","sequence":"additional","affiliation":[{"name":"Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Curtin University School of Biomedical Sciences and the Western Australian Institute of Medical Research, Molecular Immunology Group, Perth, Western Australia, 6000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Kinnear","sequence":"additional","affiliation":[{"name":"Curtin University School of Biomedical Sciences and the Western Australian Institute of Medical Research, Molecular Immunology Group, Perth, Western Australia, 6000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Cooperative Research Centre for Oral Health Science, Melbourne Dental School, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4689-4698.2004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.2804-2809.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.8080"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6611"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1991.tb00479.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1992.tb01666.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208100608"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0765.2002.01364.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06207.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05401.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.654-658.1986"},{"key":"e_1_3_2_13_2","first-page":"308","volume":"95","year":"1987","unstructured":"Larjava, H., V. 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