eISSN: 2299-0046
ISSN: 1642-395X
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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5/2022
vol. 39
 
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abstract:
Original paper

Simulated in vitro hypoxic conditions from psoriatic arthritis cartilage change plasminogen activating system urokinase and serpine functionality. Reversal of antiapoptotic protection suggests common homeostatic buffering

Michal Nohawica
1
,
Agnieszka Nowak-Terpilowska
2
,
Kinga Adamska
3
,
Marzena Wyganowska-Swiatkowska
3

  1. Department of Dental Surgery and Periodontology, Poznan University of Medical Sciences, Poznan, Poland
  2. Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland
  3. Department of Dermatology and Venereology, Poznan University of Medical Sciences, Poznan, Poland
Adv Dermatol Allergol 2022; XXXIX (5): 944-952
DOI: https://doi.org/10.5114/ada.2022.113405
Online publish date: 2022/02/08
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Introduction
Rheumatoid and psoriatic arthritis are both characterised by synovial destruction associated with a higher turnover of the extracellular matrix. In both conditions, inflammatory processes create hypoxic environments which destabilise members of the plasminogen activating system.

Aim
Comparing the effect of bioactive concentrations of urokinase (uPA) and serpine (PAI-1) on cellular survival of human fibroblast-like-synoviocytes (HFLS) in rich and hypoxic growth media.

Material and methods
Monocultures of HFLS were exposed to bioactive uPA and PAI-1 concentrations in both media conditions for 24, 48 and 72 h. Cellular survival was evaluated with a cell viability assay by spectrum absorbance of formazan reduced WST-8.

Results
PAI-1 at 0.1 and 1 µg/ml was found to stimulate cell viability under hypoxic stress at 48 and 72 h of incubation, with the effect increasing from 48 to 72 h. uPA increased cell viability in rich medium at 48 and 72 h of incubation between 5 and 40 ng/l, but was found to reduce viability at 80 ng/l at 24 and 48 h. PAI-1 increased cell viability in the hypoxic stress model, while high concentrations of uPA decreased cell viability in rich medium.

Conclusions
The alternative modes of function at extreme concentrations provide a novel description of PAI-1 and uPA activity based on their colocalization and mutual buffering capacity, helping to place these molecules more accurately in the context of arthritic synovial deterioration.

keywords:

synoviocytes, plasminogen activation system, rheumatoid arthritis, psoriatic arthritis, urokinase plasminogen activator, plasminogen activator inhibitors
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