title: Effects of free fatty acids on human salivary gland epithelial cells.
abstract: 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.
authors.affiliation: Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan. shikama@tokushima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Shikama
authors.forename: N
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Y
authors.initials: Y
authors.lastname: Kudo
authors.forename: Y
authors.initials: Y
authors.lastname: Bando
authors.forename: N
authors.initials: N
authors.lastname: Aki
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Funaki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis; D015603:Keratinocytes / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects; D008840:Microfilament Proteins / Q000187:drug effects; D009062:Mouth Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D012859:Sjogren's Syndrome / Q000473:pathology*; D013228:Stearates / Q000494:pharmacology; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects; D013049:Spectrin
chemical_list: D002352:Carrier Proteins; D053148:Caspase 3; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D015850:Interleukin-6; D008565:Membrane Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D010168:Palmitates; D013228:Stearates; D048051:p38 Mitogen-Activated Protein Kinases; D013049:Spectrin; C505407:CASP3 protein, human
keywords: Sjögren’s syndrome; alpha-fodrin; apoptosis; interleukin-6; lipids; palmitate