Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth.
OBJECTIVE
Intrinsic tissue regeneration mechanisms are still not fully understood. The destruction/reconstruction processes are usually in fine balance; however, this can be easily destroyed, for example in the environment of chronic inflammation. One of the major proteins present at the inflammatory sites is the multifunctional protein alpha-1-antitrypsin (AAT). In this study, potential therapeutic effects of this major human antiprotease on progenitor cells are assessed.


METHODS
Stromal cells from human exfoliated deciduous teeth (SHEDs) were used, which are similar to the mesenchymal stromal cells isolated from other tissues. SHEDs were cultivated in the presence of subphysiological, physiological and inflammatory concentrations of AAT, and their proliferation and motility traits were assayed. Some intracellular signaling pathways, AAT internalization by SHEDs and their matrix metalloprotease profile were studied in parallel.


RESULTS
Physiologic and inflammatory concentrations of AAT significantly increased the cell proliferation rate, induced phosphorylation of several key protein kinases and increased the amount of secreted active gelatinases. Moreover, cells exposed to physiologic and inflammatory levels of AAT were able to invade and migrate more efficiently. Subphysiologic AAT levels did not change cell behavior significantly.


CONCLUSIONS
AAT at physiologic and inflammatory concentrations positively modulates the proliferation and motility of SHEDs in vitro. These results suggest the importance of AAT in the maintenance and regulation of tissue progenitor cells in vivo.
Aldonyte
Ruta
R
State Institute of Science "Centre of Innovative Medicine", Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania. ruta.aldonyte@ekmi.vu.lt
Tunaitis
Virginijus
V
Surovas
Andrejus
A
Suriakaite
Kristina
K
Jarmalaviciute
Akvile
A
Magnusson
Karl-Eric
KE
Pivoriunas
Augustas
A
D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D005260:Female; D005434:Flow Cytometry; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects*; D014094:Tooth, Deciduous / Q000166:cytology* / Q000187:drug effects*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D018093:Gelatinases