title: Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth.
abstract: 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.
authors.affiliation: State Institute of Science "Centre of Innovative Medicine", Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania. ruta.aldonyte@ekmi.vu.lt
authors.forename: Ruta
authors.initials: R
authors.lastname: Aldonyte
authors.forename: Virginijus
authors.initials: V
authors.lastname: Tunaitis
authors.forename: Andrejus
authors.initials: A
authors.lastname: Surovas
authors.forename: Kristina
authors.initials: K
authors.lastname: Suriakaite
authors.forename: Akvile
authors.initials: A
authors.lastname: Jarmalaviciute
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.forename: Augustas
authors.initials: A
authors.lastname: Pivoriunas
mesh_terms: 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*
chemical_list: D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D018093:Gelatinases