NF-κB Controls Resistance of Human Salivary Gland (HSG) Cells to Apoptosis in an in Vitro Model of Sjogren’s Syndrome

Yan Wang, Syed A. Jamal, Luis F. Torres-Romero, Agostino Molteni, Alexander Shnyra, Carole McArthur

Department of Molecular Biosciences, Lawrence, USA.
Department of Oral and Craniofacial Science, School of Dentistry, Kansas City, USA.
Kansas City University of Medicine and Biosciences, Kansas City, USA.

DOI: 10.4236/ojra.2014.43025                

Abstract

Aim: To elucidate the anti-apoptotic properties of nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB) and feedback regulation of NF-κB by nuclear factor of kappa light-chain-enhancer of activated B-cells inhibitor alpha (IκBα). Methods: We developed an in vitro model of Sjogren’s syndrome by transfecting human salivary gland (HSG) and acinar cells (NS-SV-AC) with a plasmid-encoding IκBαM (pCMV-IκBαM), a degradation-resistant IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-mutant, and examined TNF-induced apoptosis and anti-apoptotic properties of NF-κB. Apoptosis and induction of pro-apoptotic and anti-apoptotic genes were investigated by cDNA arrays, RT-PCR, electrophoretic mobility shift assays, and western blot. Results: In the presence of NF-κB inhibitors, TNF-induced apoptosis was markedly increased in both salivary gland and acinar cells. Increased caspase-3 activity was present in both HSG and NS-SV-AC cells. IκBαM-transfected salivary gland cells were more sensitive to TNF-induced apoptosis than IκBαM-transfected acinar cells. Transcription of pro-apoptotic genes was confirmed in both HSG and NS-SV-AC cells that were transfected with IκBαM. Results from caspase-3 activity assay confirmed previous experiments showing an apoptotic role for NF-κB. Conclusion: Data from gene expression arrays suggest that different mechanisms may operate during TNF-induced apoptosis in salivary gland ductal and acinar cells.

Keywords

Acinar, Ductal, Cytokines, Salivary Glands, Sjogren’s Syndrome, Tumor Necrosis Factor-Alpha

Conflicts of Interest

The authors declare no conflicts of interest.

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