University of California , San Diego , La Jolla 92093-0663 , USA .
Arthritis Rheum 39 : 552-9 ( 1996)
Abstract
OBJECTIVE : The hyaluronan-binding protein TSG-6 ( tumor necrosis factor-stimulated gene 6 ) forms a stable complex with the serine protease inhibitor , inter-alpha-inhibitor , potentiates the inhibition of plasmin activity , and has antiinflammatory effects in vivo .
This study examines the expression of TSG-6 in human articular chondrocytes and cartilage .
METHODS : Human articular chondrocytes and cartilage explants were stimulated with cytokines , growth factors , and other agents .
TSG-6 expression was analyzed by imaging-assisted Northern and Western blotting .
RESULT : TSG-6 messenger RNA ( mRNA ) expression was upregulated by cytokines and growth factors , predominantly interleukin-1 beta ( IL-1 beta ) , tumor necrosis factor alpha ( TNF alpha ) , platelet-derived growth factor AA ( PDGF-AA ) , and transforming growth factor beta 1 ( TGF beta 1 ) .
TSG-6 mRNA induction by TGF beta 1 was delayed as compared with IL-1beta .
Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG-6 mRNA nor did it affect IL-1 beta-induced transcript levels .
TSG-6 mRNA induction may involve several signal transduction pathways .
The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C ( PKC)-mediated signaling .
In contrast , PKA- and Ca- dependent signals are only marginally involved as messengers leading to increased TSG-6 levels after IL-1beta and TNF alpha treatment .
In chondrocyte and cartilage organ cultures , both free TSG-6 ( 35 kd ) and the complex with inter-alpha-inhibitor ( 120 kd ) were present and upregulated by IL-1 beta , TNF alpha , or TGF beta 1 . CONCLUSION : Chondrocytes are a source of TSG-6 which may play a role in cartilage remodeling and joint inflammation .