Role of plasminogen activator inhibitor - 1 (PAI-1) in regulating the pathogenesis of S. aureus arthritis via plasminogen pathway.
Immunol Lett
; 209: 53-66, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30922783
ABSTRACT
uPA/tPA-mediated activation of plasminogen/plasmin pathway during S. aureus arthritis facilitates the invasion of phagocytes in the affected joint, induces production of cytokines and triggers inflammatory pathways. PAI-1, an effective inhibitor of both uPA and tPA, attenuates plasmin activity. Hence, the objective of our study was to evaluate the effect of exogenously administered PAI-1 on uPA/tPA-mediated activation of plasminogen/plasmin and its impact on the progression of arthritis. The mice were infected with live S. aureus and treated with PAI-1. Mice were sacrificed at 3, 9 and 15 days post infection and thereafter assessment of parameters related to arthritic destruction was done. PAI-1 administration resulted into decrement in uPA and tPA activities with a concomitant reduction in plasmin and MMP-2. A significant decrement in the joint and paw swelling with lower levels of inflammatory cytokines, RANKL and OPN activities were detected in case of early PAI-1 treatment. This study suggests administration of PAI-1 during S.aureus arthritis reduces the severity of arthritis by ameliorating uPA and plasmin-induced inflammatory responses and subsequent arthritic destruction.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasminogen
/
Staphylococcal Infections
/
Staphylococcus aureus
/
Signal Transduction
/
Arthritis, Infectious
/
Plasminogen Activator Inhibitor 1
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Immunol Lett
Year:
2019
Document type:
Article
Affiliation country: