ARTHRITIS & RHEUMATISM Vol. 54, No. 7, July 2006, pp 2295–2299 DOI 10.1002/art.21944 © 2006, American College of Rheumatology Salivary Gland Epithelial Cells A New Source of the Immunoregulatory Hormone Adiponectin Stergios Katsiougiannis, 1 Efstathia K. Kapsogeorgou, 1 Menelaos N. Manoussakis, 1 and Fotini N. Skopouli 2 Objective. Adiponectin is an adipocytokine that displays insulin-sensitizing and immunoregulatory properties. Adipocyte development in association with fibrosis is frequently detected in primary Sjo ¨gren’s syndrome lesions, connoting a healing process. The aim of this study was to examine the expression of adiponec- tin in minor salivary gland biopsy specimens obtained from patients with primary SS and controls. Methods. The expression of adiponectin in minor salivary gland biopsy specimens and in long-term– cultured non-neoplastic salivary gland epithelial cell (SGEC) lines obtained from patients with primary SS and control subjects was examined, using immunohis- tochemistry and immunoblotting, respectively. The expression of adiponectin, adiponectin receptor 1 (AdipoR1), and AdipoR2 messenger RNA (mRNA) by SGECs was investigated by reverse transcription– polymerase chain reaction. Results. Immunohistochemical analysis for adi- ponectin revealed positive staining of adipocytes from primary SS lesions as well as ductal epithelial cells from both patients with primary SS and controls. All of the SGEC lines tested were shown to express adiponectin, AdipoR1, and AdipoR2 mRNA, whereas adiponectin protein expression was detected by immunoblotting in SGECs from patients with primary SS but not in those from controls. The analysis of concentrated culture supernatants also revealed increased adiponectin ex- pression by SGECs from patients with SS compared with controls. Conclusion. Our findings provide novel evidence that adiponectin is produced by SGECs. The high constitutive expression of adiponectin by SGECs from patients with primary SS is likely attributable to aber- rant activation of these cells. Although the significance of adiponectin expression remains unknown, it is pos- sible that adiponectin functions in an autocrine manner, as suggested by concurrent expression of the relevant receptors. Adiponectin is an adipocytokine that was inde- pendently discovered by several groups of investigators, using different approaches (1). Although adiponectin was considered to be synthesized and secreted exclu- sively by adipocytes, recent data suggest that it is also produced by cells other than adipocytes (2–4). Adiponectin protein belongs to the soluble de- fense collagen superfamily and has structural homology with type VIII collagen, type X collagen, and comple- ment factor C1q (1). This hormone has been shown to possess several biologic properties, ranging from an insulin-sensitizing function to an immunomodulatory function. Indeed, results of several studies suggest that the protein acts as an inflammation-modulating factor (1–6). In addition, a regulatory role of adiponectin in the apoptotic death of many types of cells has been sug- gested (7). The function of adiponectin is mediated by its receptors, adiponectin receptor 1 (AdipoR1) and AdipoR2, which have different patterns of expression. AdipoR1 is expressed predominantly in muscle, whereas AdipoR2 is expressed in the liver (1). High levels of expression of both receptors have also been reported in human and rat pancreatic beta cells, and, in the presence 1 Stergios Katsiougiannis, BSc, Efstathia K. Kapsogeorgou, PhD, Menelaos N. Manoussakis, MD: University of Athens, Athens, Greece; 2 Fotini N. Skopouli, MD: Harokopio University, Athens, Greece. Address correspondence and reprint requests to Fotini N. Skopouli, MD, Department of Dietetics and Nutritional Science, Harokopio University, El. Venizelou 70, 17671, Kallithea, Athens, Greece. E-mail: fskopouli@hua.gr. Submitted for publication January 23, 2006; accepted in revised form March 24, 2006. 2295