ab1902

Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjögren's syndrome

H. Koski¹, A. Janin², M.G. Humphreys-Beher³, T. Sorsa⁴, M. Malmström⁵, Y.T. Konttinen⁶

¹Institute of Biomedicine, Department of Anatomy, University of Helsinki, Finland; ²Service Central d'Anatomie Pathologique, Hopital Saint Louis, Paris, France; ³Department of Oral Pathology, College of Dentistry, University of Florida, Gainesville, FL, USA; ⁴Department of Periodontology, Institute of Dentistry, University of Helsinki; ⁵Department of Oral Medicine, Institute of Dentistry, University of Helsinki; ⁶Department of Oral Medicine, Surgical Hospital, Helsinki University Central Hospital, Finland.

ABSTRACT
Objective
Modulation of TNF-a 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-a/TNFR system in various rheumatic diseases.
Tumor necrosis factor-alpha (TNF-a) affects its target cells through binding to two different receptors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and cytotoxic effects of TNF-a on various cells have been reported. In Sjšgrenös syndrome (SS) focal sialadenitis leads to salivary gland destruction and loss of function. Although TNF-a is one possible mediator in these processes, nothing is known about the spatial distribution of TNF-a 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-a, TNFR-p55 and TNFR-p75.

Results
TNF-a, 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-a and TNFR expression. In addition, resident vascular endothelial cells, ductal epithelial cells and fibroblasts co-expressed TNF-a and TNFR. In contrast, acinar end piece cells did not express TNF-a or TNFR-p75 although TNFR-p55 was expressed.

Conclusion
The interrelated localization of TNF receptors and their ligand TNF-a in inflammatory and in endothelial cells suggests a proinflammatory role of TNF-a in SS. The expression of TNF-a 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-a/TNRF system argues against its role in acinar cell atrophy.

Key words
Sjögren's syndrome, TNF-a, receptor, apoptosis, atrophy, acinar cell.

Please address correspondence and reprint requests to: Dr. Hannele Koski, Institute of Biomedicine, Department of Anatomy, PO Box 9 (Siltavuorenpenger 20 A), FIN-00014 University of Helsinki, Finland.
E-mail: hannele.koski@helsinki.fi