NLRC5 limits the activation of inflammatory pathways
| Autor: | Joao G. Magalhaes, Szilvia Benko, Stephen E. Girardin, Dana J. Philpott |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Immunology Molecular Sequence Data Jurkat cells NLR Proteins Proinflammatory cytokine Cell Line Jurkat Cells Mice NLRC5 Cell Line Tumor Immunology and Allergy Animals Humans Amino Acid Sequence NLRX1 Inflammation CD40 Innate immune system biology Macrophages Intracellular Signaling Peptides and Proteins Cell biology Interleukin-10 biology.protein Tumor necrosis factor alpha Caco-2 Cells Inflammation Mediators HeLa Cells Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 185(3) |
| ISSN: | 1550-6606 |
| Popis: | Nod-like receptors (NLRs) are intracellular sentinel proteins that are implicated in the detection of microbes and danger signals, thereby controlling several key innate immune pathways. The human genome encodes 22 NLR proteins, the function of many of which remains unknown. In this study, we present the identification and characterization of NLRC5, a NLR protein whose expression is found predominantly in cells of the myeloid and lymphoid lineages. NLRC5 expression was strongly induced by IFN-γ and more modestly by LPS and polyinosinic:polycytidylic acid. Overexpression of NLRC5 in HEK293T cells resulted in a global dampening of NF-κB–, AP-1–, and type I IFN-dependent signaling, most likely through transcriptional repression. Accordingly, NLRC5 was found to shuttle between the cytosol and the nucleus in a CrmA-dependent manner. Knocking down NLRC5 expression in RAW264.7 murine macrophages resulted in a potent upregulation of the proinflammatory responses to IFN-γ and LPS, including increased secretion of TNF, IL-6, and IL-1β, as well as cell surface expression of CD40. Strikingly, NLRC5 expression was also found to be critical for LPS-induced IL-10 production in RAW264.7 macrophages. Collectively, our results identify NLRC5 as a negative modulator of inflammatory pathways. |
| Databáze: | OpenAIRE |
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