AJP - Cell Physiology, Vol 263, Issue 1 C24-C29, Copyright © 1992 by American Physiological Society
Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts
T. J. Smith, A. Ahmed, M. G. Hogg and P. J. Higgins
Division of Molecular and Cellular Medicine, Albany Medical College, New York.
Expression of plasminogen activator inhibitor type 1 (PAI-1), an important
determinant of the pericellular proteolytic environment, was assessed in
cultured human orbital and dermal fibroblasts. Bidimensional
electrophoretic separation of total cellular [35S]methionine-labeled
proteins revealed multiple isoforms of the 50-kDa PAI-1 protein
(isoelectric point range 5.6-6.3) expressed in dermal strains but not in
orbital cultures. The addition of human recombinant interferon-gamma (100
U/ml) to the media for 48 h resulted in a marked induction of PAI-1 in the
orbital cultures (greater than 50-fold above baseline), whereas the
expression in dermal cultures was either attenuated or induced modestly
(5-fold). The identity of the 50-kDa PAI-1 was verified by
immunoprecipitation of secreted proteins. Indirect immunofluorescence
localized PAI-1 to aggregates at the ventral undersurface of the monolayer.
Interferon-gamma induced several other proteins in cultured cells. The
observation that untreated orbital fibroblasts do not express detectable
cell-associated PAI-1 suggests that the pericellular proteolytic
environment of these cells is regulated ordinarily by other factors. The
economy of the extracellular matrix of orbital connective tissue may be
particularly susceptible to the influence of inflammatory cytokines such as
interferon-gamma.
