Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjögren's syndrome.
OBJECTIVE
Modulation of TNF-alpha by neutralizing antibodies, soluble receptors and TNFR: Fc fusion proteins are being developed for the therapeutic modulation of immune inflammation. It is becoming increasingly important to understand the state and involvement of the TNF-alpha/TNFR system in various rheumatic diseases. Tumor necrosis factor-alpha (TNF-alpha) affects its target cells through binding to two different receptors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and cytotoxic effects of TNF-alpha on various cells have been reported. In Sjögren's syndrome (SS) focal sialadenitis leads to salivary gland destruction and loss of function. Although TNF-alpha is one possible mediator in these processes, nothing is known about the spatial distribution of TNF-alpha in relation to its receptors/target cells in salivary gland tissue.


METHODS
Labial salivary glands (LSG) were obtained from 16 SS patients and 13 healthy controls and stained using the immunohistochemical peroxidase-anti-peroxidase (PAP) method for TNF-alpha, TNFR-p55 and TNFR-p75.


RESULTS
TNF-alpha, TNFR-p55 and TNFR-p75 staining was absent, weak or relatively inextensive in controls compared to SS patients. Infiltrating mononuclear inflammatory cells in SS patients displayed moderate to strong TNF-alpha and TNFR expression. In addition, resident vascular endothelial cells, ductal epithelial cells and fibroblasts co-expressed TNF-alpha and TNFR. In contrast, acinar end piece cells did not express TNF-alpha or TNFR-p75 although TNFR-p55 was expressed.


CONCLUSIONS
The interrelated localization of TNF receptors and their ligand TNF-alpha in inflammatory and in endothelial cells suggests a proinflammatory role of TNF-alpha in SS. The expression of TNF-alpha and its receptors in fibroblasts and ductal cells may contribute to ductal hyperplasia and glandular fibrosis. However, in contrast to expectations, the cellular localization of the TNF-alpha/TNRF system argues against its role in acinar cell atrophy.
Koski
H
H
Institute of Biomedicine, Department of Anatomy, University of Helsinki, Finland. hannele.koski@helsinki.fi
Janin
A
A
Humphreys-Beher
M G
MG
Sorsa
T
T
Malmström
M
M
Konttinen
Y T
YT
D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001284:Atrophy; D001706:Biopsy; D006801:Humans; D007124:Immunoenzyme Techniques; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II; D012469:Salivary Glands / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000276:immunology
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha