title: The inhibitory receptor toll interleukin-1R 8 (TIR8/IL-1R8/SIGIRR) is downregulated in chronic lymphocytic leukemia.
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.
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Vilia
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fonte
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Veliz Rodriguez
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tocchetti
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ranghetti
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.|b Vita-Salute San Raffaele University , Milano , Italy.
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfò
authors.affiliation: c Institute of Applied Biosciences, CERTH , Thessaloniki , Greece.|d Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.
authors.forename: Nikos
authors.initials: N
authors.lastname: Papakonstantinou
authors.affiliation: c Institute of Applied Biosciences, CERTH , Thessaloniki , Greece.|d Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Ntoufa
authors.affiliation: c Institute of Applied Biosciences, CERTH , Thessaloniki , Greece.|d Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.|b Vita-Salute San Raffaele University , Milano , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.affiliation: a Division of Experimental Oncology , IRCCS San Raffaele Scientific Institute , Milano , Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Muzio
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001374:Azacitidine / Q000008:administration & dosage; D019175:DNA Methylation; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D017472:Receptors, Interleukin-1; C546891:SIGIRR protein, human; C484529:SIGIRR protein, mouse; D001374:Azacitidine
keywords: Azacytidine; SIGIRR; TIR8; Toll like receptors; chronic lymphocytic leukemia; toll interleukin-1 receptor 8