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AB0053 Ikba regulatory protein is downregulated in sjögren’s syndrome salivary gland epithelial cells.
  1. M. D’amore1,
  2. S. Lisi2,
  3. R. De Lucro2,
  4. D. Ribatti2,
  5. M. Sisto2
  1. 1DIM
  2. 2SMBNOS, University of Bari, Bari, Italy

Abstract

Background The transcription factor nuclear factor-κB (NF-κB) pathway has long been considered a prototypical pro-inflammatory signalling pathway, largely based on the role of NF-κB in the expression of pro-inflammatory genes including cytokines, chemokines, and adhesion molecules. The NF-κB pathway does indeed regulate pro-inflammatory cytokine production, leukocyte recruitment, or cell survival, which are important contributors to the inflammatory response during the development of autoimmune diseases. Although aberrant regulation in the NF-κB signal transduction pathway involving the inhibitory IκBa was observed in several autoimmune disorders, thereis presently nopublication investigating the alteration of IκBα expression in human salivary gland epithelial cells (SGEC) from SS patients.

Objectives In this study we examine the expression of the NF-κB inhibitory protein termed IκBα in SGEC comparing it with SGEC from healthy controls, to test the hypothesis that an altered expression of IκBα occurs in SGEC from SS biopsies.

Methods RT-PCR, Real Time-PCR, western blot, immunohistochemistry and flow cytometry were employed to examine the expression IκBα in SS biopsies in comparison with salivary gland biopsies from healthy subjects.

Results Changes in the levels of IκBαin SS SGEC in comparison with healthy subjects were demonstrated, suggesting that the attenuated expression of IκBα could contribute to the deregulation of NF-κB pathways in SS. Given its key function in the fine-tuning of NF-κB signalling, it was to be expected that defects in IκBα expression or function could lead to chronic inflammation and tissue damage. In line with gene and protein analysis results, we delineated the changes in IκBα both at gene and protein expression levels, finding a clear reduction of IκBα in tissue samples from active Sjögren’s syndrome patients in comparison with healthy subjects. In biopsy specimens, we found a moderate positive staining for the IκBα protein in healthy controls examined in theimmunohistochemical study, located in the cytoplasm of acini and ductal cells. Conversely, SS salivary gland biopsies elicited a weak cytoplasmic positivity for IκBα.

Conclusions The analysis of IκBα expression at salivary gland epithelial cell level could be a potential new hallmark of SS progression and sustain a rationale to more deeply investigate the therapeutic potential of specific NF-κB inhibitors in SS.

Disclosure of Interest None Declared

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