Differentiation-dependent and stimulus-specific expression of ILA, the human 4-1BB-homologue, in cells of mesenchymal origin.
OBJECTIVE
Examine the expression of ILA, a member of the human NGF/TNF receptor family and the homologue of the murine 4-1BB, in mesenchymal cells.


METHODS
ILA mRNA was analyzed by quantitative polymerase chain reaction and Northern blotting in human articular chondrocytes and fibroblasts. ILA protein expression was examined by flow cytometry.


RESULTS
The proinflammatory stimuli interleukin-1 beta (IL-1 beta), tumour necrosis factor (TNF) alpha, leukemia inhibitory factor (LIF), interferon (IFN) gamma and lipopolysaccharide (LPS) induced ILA mRNA in primary human articular chondrocytes. TGF beta and dexamethasone inhibited IL-1 induced ILA expression. Chondrocytes expressed the 4.8, 4.0 and 1.9 kb isoforms of ILA mRNA which had previously been observed in lymphocytes and additional isoforms at 3.2, 1.5 and 1.2 kb. Cycloheximide alone induced ILA mRNA in primary chondrocytes while the combination of IL-1 and cycloheximide resulted in ILA superinduction. In contrast to primary chondrocytes, activated human synovial or skin fibroblasts did not express ILA mRNA. Furthermore, ILA was no longer inducible by IL-1 in subcultured, dedifferentiated chondrocytes. However, repression of ILA in fibroblasts and dedifferentiated chondrocytes was overcome by cycloheximide and IL-1 further increased ILA mRNA levels in the presence of cycloheximide. Flow cytometric analysis of ILA protein expression with monoclonal antibodies revealed increased cell-surface expression on IL-1 or TNF alpha, but not on TGF beta stimulated chondrocytes.


CONCLUSIONS
ILA is not only expressed in the immune system but also in mesenchymal cells. ILA expression is induced by specific stimuli and modulated by the differentiation status of the cells. ILA can serve as a model and marker to analyze differentiation-dependent gene expression in mesenchymal cells.
von Kempis
J
J
Department of Medicine, UCSD, La Jolla, USA.
Schwarz
H
H
Lotz
M
M
D002358:Cartilage, Articular / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D008648:Mesoderm / Q000166:cytology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013583:Synovial Membrane / Q000166:cytology
D016207:Cytokines; C084945:ILA receptor; D007375:Interleukin-1; D012333:RNA, Messenger; D018121:Receptors, Cytokine