title: Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR.
abstract: TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor family. The present study was designed to investigate the expression and function of TIR8. TIR8 was mainly expressed in mouse and human epithelial tissues such as kidney, lung and gut. Resting and activated T and B lymphocytes and monocytes-macrophages expressed little or no TIR8, with the exception of the mouse GG2EE macrophage line. In the kidney, the organ with highest mRNA levels, TIR8 expression was confined to epithelial cells and, in situ, to tubular epithelium. A variety of signals failed to regulate TIR8 expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter system was used to investigate the function of TIR8. TIR8 did not activate NF-kB expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but the extracellular domain was dispensable for blocking activity. Thus, TIR8 is a unique member of the IL-1R family, with a distinct pattern of epithelial expression, including the kidney and mucosae, and an inhibitory function on IL-1 signaling.
authors.affiliation: Dept. Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Milan, 20157, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Polentarutti
authors.forename: Giselle Penton
authors.initials: GP
authors.lastname: Rol
authors.forename: Marta
authors.initials: M
authors.lastname: Muzio
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
authors.forename: Marco
authors.initials: M
authors.lastname: Camnasio
authors.forename: Federica
authors.initials: F
authors.lastname: Riva
authors.forename: Carla
authors.initials: C
authors.lastname: Zoja
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Susanna
authors.initials: S
authors.lastname: Tomasoni
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D015536:Down-Regulation; D017930:Genes, Reporter; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; C484529:SIGIRR protein, mouse