α1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: Serpinolytic inhibition by doxycycline

H. M. Lee, L. M. Golub, D. Chan, M. Leung, K. Schroeder, M. Wolff, S. Simon, R. Crout

Research output: Contribution to journalArticle

Abstract

The serum protein, α1-proteinase inhibitor (α1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human α1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. α1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact α1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, α1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and α1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the α1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting α1-PI regulation of elastase and other serineproteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for α1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalJournal of Periodontal Research
Volume32
Issue number1 PART 1
DOIs
StatePublished - Jan 1997

Keywords

  • Adult periodontitis
  • Doxycycline
  • Gingival crevicular fluid
  • α-proteinase inhibitor

ASJC Scopus subject areas

  • Periodontics

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