RRC ID 67887
Author Ueno-Shuto K, Kato K, Tasaki Y, Sato M, Sato K, Uchida Y, Sakai H, Ono T, Suico MA, Mitsutake K, Tokutomi N, Kai H, Shuto T.
Title Lipopolysaccharide decreases single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) expression by suppressing specificity protein 1 (Sp1) via the Toll-like receptor 4 (TLR4)-p38 pathway in monocytes and neutrophils.
Journal J Biol Chem
Abstract Single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) is one of the immunoglobulin-like membrane proteins that is crucial for negative regulation of toll-like receptor 4 (TLR4) and interleukin-1 receptor. Despite the importance of understanding its expression and function, knowledge is limited on the regulatory mechanism in the epithelial tissues, such as the liver, lung, and gut, where its predominant expression is originally described. Here, we found expression of SIGIRR in non-epithelial innate immune cells, including primary peripheral blood monocytes, polymorphonuclear neutrophils, monocytic RAW264 cells, and neutrophilic-differentiated HL-60 cells. Consistent with previous findings in epithelial tissues, SIGIRR gene and protein expression were also down-regulated by LPS treatment in a time-dependent manner in primary blood monocytes and polymorphonuclear neutrophils. A reduction was also observed in RAW264 and differentiated HL-60 cells. Notably, exogenous introduction of the dominant negative form of TLR4 and siRNA of p38 resulted in inhibition of LPS-induced SIGIRR down-regulation, whereas treatment with p38 activator anisomycin showed a dose-dependent decrease in SIGIRR expression, suggesting TLR4-p38 signal as a critical pathway for LPS-induced SIGIRR down-regulation. Finally, reporter gene and chromatin immunoprecipitation assays demonstrated that Sp1 is a key factor that directly binds to the proximal promoter of SIGIRR gene and consequently regulates basal SIGIRR expression, which is negatively regulated by the LPS-dependent TLR4-p38 pathway. In summary, the data precisely demonstrate how LPS down-regulates SIGIRR expression and provide a role of LPS signal that counteracts Sp1-dependent basal promoter activation of SIGIRR gene via TLR4-p38 pathway in non-epithelial innate immune cells.
Volume 289(26)
Pages 18097-109
Published 2014-6-27
DOI 10.1074/jbc.M113.532093
PII S0021-9258(20)40522-8
PMID 24821721
PMC PMC4140261
MeSH Animals Base Sequence Down-Regulation Humans Lipopolysaccharides / metabolism* MAP Kinase Signaling System* Mice Mice, Inbred C3H Molecular Sequence Data Monocytes / metabolism* Neutrophils / metabolism* Promoter Regions, Genetic Receptors, Interleukin-1 / genetics* Receptors, Interleukin-1 / metabolism* Sp1 Transcription Factor / genetics* Sp1 Transcription Factor / metabolism Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / metabolism*
IF 4.238
Human and Animal Cells RAW 264(RCB0535)