PMID- 21943709 OWN - NLM STAT- MEDLINE DCOM- 20111220 LR - 20220321 IS - 1872-9142 (Electronic) IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 49 IP - 1-2 DP - 2011 Oct TI - Cell type and gender-dependent differential regulation of the p202 and Aim2 proteins: implications for the regulation of innate immune responses in SLE. PG - 273-80 LID - 10.1016/j.molimm.2011.08.022 [doi] AB - 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-1beta 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-alpha treatment and the expression is, in part, STAT1-dependent. However, treatment of splenic T or B cells with IFN-alpha 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-alpha 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. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Panchanathan, Ravichandran AU - Panchanathan R AD - Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, United States. FAU - Duan, Xin AU - Duan X FAU - Arumugam, Muthuvel AU - Arumugam M FAU - Shen, Hui AU - Shen H FAU - Liu, Hongzhu AU - Liu H FAU - Choubey, Divaker AU - Choubey D LA - eng GR - R01 AI066261/AI/NIAID NIH HHS/United States GR - R01 AI066261-06/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110923 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Aim2 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Ifi202b protein, mouse) RN - 0 (Inflammasomes) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Nuclear Proteins) SB - IM MH - Animals MH - B-Lymphocytes/immunology/metabolism MH - DNA-Binding Proteins MH - Female MH - Gene Expression Regulation/genetics/*immunology MH - Immunity, Innate/genetics/*immunology MH - Immunoblotting MH - Inflammasomes/immunology/metabolism MH - Intracellular Signaling Peptides and Proteins/genetics/immunology/*metabolism MH - Lupus Erythematosus, Systemic/genetics/*immunology MH - Macrophages/immunology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nuclear Proteins/*biosynthesis/genetics/immunology MH - Real-Time Polymerase Chain Reaction MH - T-Lymphocytes/immunology/metabolism PMC - PMC3211081 MID - NIHMS323955 COIS- Conflict of interest None EDAT- 2011/09/29 06:00 MHDA- 2011/12/21 06:00 PMCR- 2012/10/01 CRDT- 2011/09/28 06:00 PHST- 2011/07/18 00:00 [received] PHST- 2011/08/27 00:00 [accepted] PHST- 2011/09/28 06:00 [entrez] PHST- 2011/09/29 06:00 [pubmed] PHST- 2011/12/21 06:00 [medline] PHST- 2012/10/01 00:00 [pmc-release] AID - S0161-5890(11)00737-1 [pii] AID - 10.1016/j.molimm.2011.08.022 [doi] PST - ppublish SO - Mol Immunol. 2011 Oct;49(1-2):273-80. doi: 10.1016/j.molimm.2011.08.022. Epub 2011 Sep 23.