Cell type and gender-dependent differential regulation of the p202 and Aim2 proteins: Implications for the regulation of innate immune responses in SLE
| Autor: | Hongzhu Liu, Xin Duan, Ravichandran Panchanathan, Muthuvel Arumugam, Divaker Choubey, Hui Shen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Inflammasomes T-Lymphocytes Immunoblotting Immunology Biology Real-Time Polymerase Chain Reaction Article Mice AIM2 medicine Animals Lupus Erythematosus Systemic Nuclear protein Molecular Biology Ifi202 Regulation of gene expression B-Lymphocytes Innate immune system Macrophages Intracellular Signaling Peptides and Proteins Nuclear Proteins Inflammasome Molecular biology Immunity Innate Cell biology DNA-Binding Proteins Mice Inbred C57BL Gene Expression Regulation TLR3 Female Signal transduction medicine.drug |
| Zdroj: | Molecular Immunology. 49:273-280 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2011.08.022 |
| Popis: | Upon sensing cytosolic double-stranded DNA (dsDNA), the murine Aim2 (encoded by the Aim2 gene) protein forms an inflammasome and promotes the secretion of proinflammatory cytokines, such as IL-1β and IL-18. In contrast, the p202 protein (encoded by the Ifi202 gene) does not form an inflammasome. Previously, we have reported that the interferon (IFN) and female sex hormone-induced increased nuclear levels of p202 protein in immune cells are associated with increased susceptibility to develop a lupus-like disease. However, signaling pathways that regulate the expression of Aim2 protein remain unknown. Here we report that the expression of Aim2 gene is induced in bone marrow-derived macrophages (BMDMs) by IFN-α treatment and the expression is, in part, STAT1-dependent. However, treatment of splenic T or B cells with IFN-α or their stimulation, which induced the expression of Ifi202 gene, did not induce the expression of Aim2 gene. Furthermore, treatment of cells with the male hormone androgen increased levels of Aim2 mRNA and protein. Moreover, treatment of murine macrophage cell lines (RAW264.7 and J774A.1) with IFN-α differentially induced the expression of Aim2 and p202 proteins and regulated their sub-cellular localization. Additionally, activation of Toll-like receptors (TLR3, 4, and 9) in BMDMs and cell lines also differentially regulated the expression of Aim2 and Ifi202 genes. Our observations demonstrate that cell type and gender-dependent factors differentially regulate the expression of the Aim2 and p202 proteins, thus, suggesting opposing roles for these two proteins in innate immune responses in lupus disease. |
| Databáze: | OpenAIRE |
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