COMPETENCE FOR COLLAGENASE GENE-EXPRESSION BY TISSUE FIBROBLASTS REQUIRES ACTIVATION OF AN INTERLEUKIN-1-ALPHA AUTOCRINE LOOP

被引:94
作者
WESTMAYS, JA
STRISSEL, KJ
SADOW, PM
FINI, ME
机构
[1] MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129
[2] HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129
关键词
D O I
10.1073/pnas.92.15.6768
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The enzyme collagenase (EC 3.4.24.7), a key mediator in biological remodeling, can be induced in early-passage fibroblasts by a wide variety of agents and conditions. In contrast, at least some primary tissue fibroblasts are incompetent to synthesize collagenase in response to many of these stimulators. In this study, we investigate mechanisms controlling response to two of the conditions in question: (i) trypsin or cytochalasin B, which disrupt actin stress fibers, or (ii) phorbol 12-myristate 13-acetate (PMA), which activates growth factor signaling pathways. We demonstrate that collagenase expression stimulated by trypsin or cytochalasin B is regulated entirely through an autocrine cytokine, interleukin 1 alpha (IL-1 alpha). The IL-1 alpha intermediate also constitutes the major mechanism by which PMA stimulates collagenase expression, although a second signaling pathway(s) contributes to a minor extent. Elevation of the IL-1 alpha level in response to stimulators is found to be sustained by means of an autocrine feedback loop in early-passage fibroblast cultures. In contrast, fibroblasts freshly isolated from the tissue are incompetent to activate and sustain the IL-1 alpha feedback loop, even though they synthesize collagenase in response to exogenous IL-1. We conclude that this is the reason why tissue fibroblasts are limited, in comparison with subcultured fibroblasts, in their capacity to synthesize collagenase. Activation of the IL-1 alpha feedback loop, therefore, seems likely to be an important mechanism by which resident tissue cells adopt the remodeling phenotype.
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页码:6768 / 6772
页数:5
相关论文
共 37 条
[1]   CHANGES IN CELL-SHAPE CORRELATE WITH COLLAGENASE GENE-EXPRESSION IN RABBIT SYNOVIAL FIBROBLASTS [J].
AGGELER, J ;
FRISCH, SM ;
WERB, Z .
JOURNAL OF CELL BIOLOGY, 1984, 98 (05) :1662-1671
[2]  
Alexander CM, 1991, CELL BIOL EXTRACELLU, P255
[3]  
ALLEN RW, 1987, J BIOL CHEM, V262, P649
[4]   PHORBOL ESTER INDUCIBLE GENES CONTAIN A COMMON CIS ELEMENT RECOGNIZED BY A TPA-MODULATED TRANS-ACTING FACTOR [J].
ANGEL, P ;
IMAGAWA, M ;
CHIU, R ;
STEIN, B ;
IMBRA, RJ ;
RAHMSDORF, HJ ;
JONAT, C ;
HERRLICH, P ;
KARIN, M .
CELL, 1987, 49 (06) :729-739
[5]   BIOLOGICAL PROPERTIES OF RECOMBINANT HUMAN MONOCYTE-DERIVED INTERLEUKIN-1 RECEPTOR ANTAGONIST [J].
AREND, WP ;
WELGUS, HG ;
THOMPSON, RC ;
EISENBERG, SP .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (05) :1694-1697
[6]  
BIRKEDALHANSEN H, 1992, MATRIX METALLOPROTEI
[7]  
BRINCKERHOFF CE, 1987, DEV DIS CARTILAGE BO, V4, P299
[8]  
CANNON JG, 1989, J IMMUNOL, V142, P2299
[9]   PURIFICATION OF A FACTOR FROM HUMAN-BLOOD MONOCYTE-MACROPHAGES WHICH STIMULATES THE PRODUCTION OF COLLAGENASE AND PROSTAGLANDIN-E2 BY CELLS CULTURED FROM RHEUMATOID SYNOVIAL TISSUES [J].
DAYER, JM ;
STEPHENSON, ML ;
SCHMIDT, E ;
KARGE, W ;
KRANE, SM .
FEBS LETTERS, 1981, 124 (02) :253-256
[10]  
DINARELLO CA, 1989, CRIT REV IMMUNOL, V9, P1