Differential regulation of IL-23 production in M1 macrophages by TIR8/SIGIRR through TLR4- or TLR7/8-mediated signaling. (November 2017)

• Record Type: Journal Article
• Authors: Yamaguchi, Rui; Sakamoto, Arisa; Yamamoto, Takatoshi; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo
• Is Part Of: Cytokine. Volume 99(2017)
• Page Start: 310
• Page End: 315
• Publication Date: 2017-11
• Subjects: Granulocyte–macrophage colony-stimulating factor -- IL-12p40 -- IL-23 -- Interferon regulatory factor 5 -- Single immunoglobulin interleukin-1 receptor-related molecule; ELISA enzyme-linked immunosorbent assay -- GM−CSF granulocytemacrophage colony-stimulating factor -- HNE human neutrophil elastase -- IL interleukin -- IRF interferon regulatory factor -- KLF2 kruppel-like factor 2 -- LPS lipopolysaccharide -- MAPK mitogen-activated protein kinase -- PAR protease-activated receptor -- SIGIRR single immunoglobulin interleukin-1 receptor-related molecule -- siRNA small interfering RNA -- SP1 specificity protein 1 -- TIR toll/interleukin-1 receptor -- TLR toll-like receptor -- TRAF6 tumor necrosis factor receptor-associated factor 6; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2017.08.014
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: SIGIRR is a negative regulator of TLR4 signaling. SIGIRR is a positive regulator of TLR7/8 signaling. SIGIRR deficiency promotes IRF4 expression. SIGIRR deficiency modulates IL-23 expression via IRF4. Abstract: Cross-talks between toll-like receptors (TLRs) including various negative regulatory mechanisms are many unknown. We investigated the differential mechanism of IL-23 production in M1 macrophages by single immunoglobulin interleukin-1 receptor-related (SIGIRR) molecule through TLR4 or TLR7/8. IL-12p40 production by M1 macrophages pretreated with human neutrophil elastase (HNE) was synergistically enhanced IL-12p40, but not IL-23 production, after exposure to lipopolysaccharide (LPS). LPS (a TLR4 agonist) induced a slight increase of IL-23 production, while Resiquimod (a TLR7/8 agonist) significantly enhanced IL-23 production. Expression of SIGIRR protein, a negative regulator of TLR4, was higher in M1 macrophages than in monocytes. Interestingly, SIGIRR siRNA induced a slight increment of IL-23 production after exposure of macrophages to LPS, while IL-23 production in response to Resiquimod was significantly upregulated by SIGIRR siRNA. Silencing SIGIRR enhanced IRF4 protein level determined by western blotting or ELISA. IRF4 siRNA dramatically restored IL-23 production after exposure to Resiquimod in macrophages transfected with SIGIRR siRNA. In conclusion, production of IL-23 is differentially regulated in M1 macrophages by SIGIRR through TLR4- or TLR7/8-mediated signaling. SIGIRR is both a negative regulator of TLR4 and a positive regulator of TLR7/8.