TY - JOUR
T1 - α1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis
T2 - Serpinolytic inhibition by doxycycline
AU - Lee, H. M.
AU - Golub, L. M.
AU - Chan, D.
AU - Leung, M.
AU - Schroeder, K.
AU - Wolff, M.
AU - Simon, S.
AU - Crout, R.
PY - 1997/1
Y1 - 1997/1
N2 - 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.
AB - 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.
KW - Adult periodontitis
KW - Doxycycline
KW - Gingival crevicular fluid
KW - α-proteinase inhibitor
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U2 - 10.1111/j.1600-0765.1997.tb01377.x
DO - 10.1111/j.1600-0765.1997.tb01377.x
M3 - Article
C2 - 9085238
AN - SCOPUS:0030632754
SN - 0022-3484
VL - 32
SP - 9
EP - 19
JO - Journal of Periodontal Research
JF - Journal of Periodontal Research
IS - 1 PART 1
ER -