Effects of Free Fatty Acids on Human Salivary Gland Epithelial Cells

Obesity and type 2 diabetes (T2D) are characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Primary Sjögren’s syndrome (SS) is an autoimmune disease characterized by inflammatory mononuclear cell infiltration and destruction of epithelial cells in the salivary and lacrimal glands. IL-6 production and α-fodrin degradation are increased in salivary gland epithelial cells of patients with primary SS. Although previous studies have shown a link between SS and either dyslipidemia or T2D, little is known about the clinical significance of FFAs in primary SS. Here we report that SFAs, but not unsaturated fatty acids, induced IL-6 production via NF-κB and p38 MAPK activation in human salivary gland epithelial cells. Moreover, palmitate induced apoptosis and α-fodrin degradation by caspase-3 activation. Unlike salivary gland epithelial cells, induction of IL-6 production and the degradation of α-fodrin in response to palmitate were undetectable in squamous carcinoma cells and keratinocytes. Taken together, SFAs induced IL-6 production and α-fodrin degradation in salivary gland epithelial cells, implicating a potential link between the pathogenesis of primary SS and SFAs level in plasma.