Activation of AMP-Activated Protein Kinase by Adiponectin Rescues Salivary Gland Epithelial Cells From Spontaneous and Interferon-gamma-Induced Apoptosis

作者：Katsiougiannis Stergios; Tenta Roxane; Skopouli Fotini N^*

来源：Arthritis and Rheumatism, 2010, 62(2): 414-419.

DOI：10.1002/art.27239

Objective. Primary Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltrates associated with destruction of salivary gland epithelial cells (SGECs) induced mainly by apoptosis. Adiponectin is an immunoregulatory hormone. We have previously shown that SGECs from patients with primary SS as well as from controls differentially express adiponectin. SGECs derived from patients with primary SS constitutively produce and secrete adiponectin in higher quantities. The aim of this study was to investigate the effect of adiponectin on the proliferation and apoptosis of SGECs.
Methods. Cultured, non-neoplastic SGECs were treated with recombinant human adiponectin, and the rate of cell proliferation was assessed. Spontaneous and interferon-gamma (IFN gamma)-induced apoptosis was evaluated with a specific single-stranded DNA enzyme-linked immunosorbent assay. The AMP-activated protein kinase (AMPK) inhibitor Compound C was used to test the involvement of AMPK in adiponectin effects. Western blotting was applied to detect the phosphorylation levels of AMPK after adiponectin treatment.
Results. Adiponectin treatment resulted in a dose-dependent suppression of proliferation of SGECs from patients with primary SS and control donors. Adiponectin protected cells from spontaneous as well as from IFN gamma-induced apoptosis. Furthermore, the antiapoptotic effects of adiponectin were dependent upon AMPK phosphorylation at Thr(172), since pretreatment of SGECs with Compound C abolished the adiponectin protective effect.
Conclusion. Adiponectin exerted antiproliferative effects on SGECs without inducing apoptosis and protected SGECs from spontaneous as well as from IFN gamma-induced apoptosis through an AMPK-dependent pathway. Our observations suggest that adiponectin may protect SGECs in this specific inflammatory milieu, providing a potential pathway through which AMPK may regulate cell survival under energy stress conditions such as autoimmune inflammation.

• 出版日期2010-2