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-BETA AND BASIC FIBROBLAST GROWTH-FACTOR

被引：28

作者：

CAMPBELL, IK ^{[1
]}

WOJTA, J ^{[1
]}

NOVAK, U ^{[1
]}

HAMILTON, JA ^{[1
]}

机构：

[1] ROYAL MELBOURNE HOSP,DEPT DIAGNOST HAEMATOL,PARKVILLE,VIC,AUSTRALIA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 1994年 / 1226卷 / 03期

基金：

奥地利科学基金会;

关键词：

CARTILAGE; CHONDROCYTE; CYTOKINE; ARTHRITIS; PLASMINOGEN ACTIVATOR; PROTEINASE INHIBITOR;

D O I：

10.1016/0925-4439(94)90038-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：277 / 285

页数：9

共 57 条

[21] TISSUE COOPERATION IN A PROTEOLYTIC CASCADE ACTIVATING HUMAN INTERSTITIAL COLLAGENASE
HE, CS
WILHELM, SM
PENTLAND, AP
MARMER, BL
GRANT, GA
EISEN, AZ
GOLDBERG, GI
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) : 2632 - 2636
[22] TRANSFORMING GROWTH FACTOR-BETA-1 IS A POTENT INDUCER OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN HUMAN GLIOBLASTOMA AND CARCINOMA CELL-LINES
HELSETH, E
DALEN, A
UNSGAARD, G
SKANDSEN, T
GRONDAHLHANSEN, J
LUND, LR
[J]. APMIS, 1988, 96 (09) : 845 - 849
[23] STIMULATION OF CARTILAGE-MATRIX PROTEOGLYCAN SYNTHESIS BY MORPHOLOGICALLY TRANSFORMED CHONDROCYTES GROWN IN THE PRESENCE OF FIBROBLAST GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-BETA
INOUE, H
KATO, Y
IWAMOTO, M
HIRAKI, Y
SAKUDA, M
SUZUKI, F
[J]. JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 138 (02) : 329 - 337
[24] KIKUCHI H, 1987, J RHEUMATOL, V14, P439
[25] PLASMINOGEN-ACTIVATOR INHIBITOR IS ASSOCIATED WITH THE EXTRACELLULAR-MATRIX OF CULTURED BOVINE SMOOTH-MUSCLE CELLS
KNUDSEN, BS
HARPEL, PC
NACHMAN, RL
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1987, 80 (04) : 1082 - 1089
[26] ACTION OF PLASMIN ON CARTILAGE
LACK, CH
ROGERS, HJ
[J]. NATURE, 1958, 182 (4640) : 948 - 949
[27] LAIHO M, 1987, J BIOL CHEM, V262, P17467
[28] LAIHO M, 1989, CANCER RES, V49, P2533
[29] INTERLEUKIN-1-BETA AND INTERLEUKIN-1-ALPHA STIMULATE THE PLASMINOGEN-ACTIVATOR ACTIVITY AND PROSTAGLANDIN-E2 LEVELS OF HUMAN SYNOVIAL-CELLS
LEIZER, T
CLARRIS, BJ
ASH, PE
VANDAMME, J
SAKLATVALA, J
HAMILTON, JA
[J]. ARTHRITIS AND RHEUMATISM, 1987, 30 (05): : 562 - 566
[30] STRUCTURE OF THE HUMAN-PLASMINOGEN ACTIVATOR INHIBITOR-1 GENE - NONRANDOM DISTRIBUTION OF INTRONS
LOSKUTOFF, DJ
LINDERS, M
KEIJER, J
VEERMAN, H
VANHEERIKHUIZEN, H
PANNEKOEK, H
[J]. BIOCHEMISTRY, 1987, 26 (13) : 3763 - 3768

← 1 2 3 4 5 6 →