Toll-like receptor 3 stimulation promotes Ro52/ TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway.

Autor: Kyriakidis, N. C., Kapsogeorgou, E. K., Gourzi, V. C., Konsta, O. D., Baltatzis, G. E., Tzioufas, A. G.
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Zdroj: Clinical & Experimental Immunology; Dec2014, Vol. 178 Issue 3, p548-560, 13p, 2 Color Photographs, 5 Graphs
Abstrakt: Up-regulated expression of Ro52/tripartite motif-containing protein 21 ( TRIM21), Ro60/TROVE domain family, member 2 ( TROVE2) and lupus LA protein/Sjögren's syndrome antigen B ( La/ SSB) autoantigens has been described in the salivary gland epithelial cells ( SGEC) of patients with Sjögren's syndrome ( SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional Toll-like receptor ( TLR)-3, whereas Ro52/ TRIM21 negatively regulates TLR-3-mediated inflammation. Herein, we investigated the effect of TLR-3-signalling on the expression of Ro52/ TRIM21, as well as Ro60/ TROVE2 and La/ SSB autoantigens, by SGECs. The effect of TLR-3 or TLR-4 stimulation on autoantigen expression was evaluated by poly I: C or lipopolysaccharide ( LPS) treatment, respectively, of SGEC lines (10 from SS patients, 12 from non- SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. Poly I: C, but not LPS, resulted in a two-step induction of Ro52/ TRIM21 mRNA expression by SGECs, a 12-fold increment at 6 h followed by a 2·5-fold increment at 24-48 h, whereas it induced a late two-fold up-regulation of Ro60/ TROVE2 and La/ SSB mRNAs at 48 h. Although protein expression levels were not affected significantly, the late up-regulation of Ro52/ TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout the nucleus. These late phenomena were mediated significantly by interferon ( IFN)-β production, as attested by cognate secretion and specific inhibition experiments and associated with IFN regulatory factor ( IRF)3 degradation. TLR-3-signalling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. TLR-3 signalling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their over-expression in inflamed tissues and possibly in their exposure to the immune system. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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