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Original Articles: Research

The inhibitory receptor toll interleukin-1R 8 (TIR8/IL-1R8/SIGIRR) is downregulated in chronic lymphocytic leukemia

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Pages 2419-2425 | Received 01 Aug 2016, Accepted 04 Feb 2017, Published online: 28 Feb 2017
 

Abstract

Toll interleukin-1 receptor 8 (also known as TIR8, SIGIRR, or IL1R8) is a transmembrane receptor that inhibits inflammation. Accordingly, genetic inactivation of this protein exacerbates chronic inflammation and inflammation-associated tumors in mice. In particular, lack of TIR8 triggers leukemia progression in a mouse model of chronic lymphocytic leukemia (CLL), supporting its role as a novel tumor restrainer. The aim of this study was to measure the amount of TIR8 mRNA and protein in CLL cells, and to analyze its regulation of expression. Circulating leukemic cells expressed lower levels of TIR8 compared to normal B-lymphocytes. Treatment of CLL cells with Azacytidine restored higher levels of TIR8 suggesting that DNA methylation may be involved in modulating TIR8 expression, with implications for novel therapeutic strategies.

Acknowledgements

We thank Prof. Federico Caligaris-Cappio for helpful suggestions and support. This work was supported by Associazione Italiana per la Ricerca sul Cancro, Milano, Italy (AIRC IG-16777 to MM and AIRC IG-15189 to PG; AIRC Special Program Molecular Clinical Oncology – 5 per mille #9965 to MM and PG), and Ricerca Finalizzata 2010 (RF-2010-2318823 to PG) – Ministero della Salute, Roma, Italy. Kostas Stamatopoulos receives unrestricted research support from Janssen Pharmaceuticals and Novartis SA.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1295142

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