Cytokine modulation of plasminogen activator inhibitor-1 (PAI-1) production by human articular cartilage and chondrocytes. Down-regulation by tumor necrosis factor alpha and up-regulation by transforming growth factor-B basic fibroblast growth factor.
Biochim Biophys Acta
; 1226(3): 277-85, 1994 Jul 18.
Article
em En
| MEDLINE
| ID: mdl-8054359
ABSTRACT
Recombinant human cytokines were examined for their effects on plasminogen activator inhibitor-1 (PAI-1) production by human articular cartilage and chondrocyte monolayer cultures. Cartilage and chondrocytes were cultured with and without added cytokines and the conditioned media assayed for PAI-1 by a specific enzyme-linked immunosorbent assay, and mRNA levels determined by Northern blot analysis. Tumor necrosis factor alpha (TNF alpha) reduced, and transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) increased, the levels of PAI-1 antigen and mRNA in the culture fluids and cell extracts, respectively. The effects of TNF alpha and TGF-beta on PAI-1 antigen levels were both time- and concentration-dependent; optimum doses being 10-100 pM TNF alpha and 0.4-0.8 nM TGF-beta, with each cytokine exerting its effect on PAI-1 antigen levels within 8 h of addition to culture. TNF alpha (and interleukin-1 alpha) also countered the effects of TGF-beta and bFGF. The anti-inflammatory drugs, indomethacin and dexamethasone, did not appear to modulate PAI-1 levels in cultures of cartilage tissue. The inhibition of PAI-1 levels by cytokines and reagents which stimulate cartilage resorption (i.e., TNF alpha, interleukin-1 alpha, retinoic acid) and enhancement by cytokines which counter it (i.e., TGF-beta, bFGF) further implicate plasminogen activator in the mechanism(s) of cartilage degradation in diseases such as arthritis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cartilagem Articular
/
Citocinas
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Fator 2 de Crescimento de Fibroblastos
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Fator de Crescimento Transformador beta
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Fator de Necrose Tumoral alfa
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Inibidor 1 de Ativador de Plasminogênio
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Artropatias
Limite:
Aged
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Austrália