KMID : 0624620150480120696
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BMB Reports 2015 Volume.48 No. 12 p.696 ~ p.701
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An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines
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Seo Jin-Won
Yang Eun-Jeong Kim Se-Hoon Choi In-Hong
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Abstract
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Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA. It stimulates pro-inflammatory cytokine and interferon production. Here we reported the expression of a novel isoform of TLR3 in human astrocyte cell lines whose message is generated by alternative splicing. The isoform represents the N-terminus of the protein. It lacks many of the leucine-rich repeat domains, the transmembrane domain, and the intracellular Toll/interleukin-1 receptor domain of TLR3. Type I interferons (interferon-¥á and interferon-¥â) induced the expression of this isoform. Exogenous overexpression of this isoform inhibited interferon regulatory factor 3, signal transducers and activators of transcription 1, and Inhibitor of kappa B¥á signaling following stimulation. This isoform of TLR3 also inhibited the production of chemokine interferon-¥ã-inducible protein 10. Our study clearly demonstrated that the expression of this isoform of TLR3 was a negative regulator of signaling pathways and that it was inducible by type I interferons. We also found that this isoform could modulate inflammation in the brain.
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KEYWORD
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Astrocyte, Interferon, Isoform, Negative regulation, TLR3
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