Macrophage GIT1 contributes to bone regeneration by regulating inflammatory response
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE144739 | GEO | 2020/02/05
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC7689802 | biostudies-literature
Project description:Macrophage GIT1 contributes to bone regeneration by regulating inflammatory response
| PRJNA604763 | ENA
Project description:Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. ChIP-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2 binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach. Gene expression in BMDMs obtained from wild-type and Keap1-CKO mice. In Keap1-CKO (Keap1 flox/flox::LysM-Cre) BMDMs, Nrf2 transcription factor is activated due to Keap1-deficiency. BMDMs were obtained by a culture of bone marrow cells in the presence of M-CSF for7 days. M1-activated BMDMs were obtained by stimulation with LPS and IFNg for 6 hours, while M2-activated BMDMs were obtained by a stimulation with IL-4 for 6 hours. Two independent BMDM cultures were performed, and each experiment contains samples obtained from one wild-type and one Keap1-CKO mice, respectively.
2016-05-12 | E-GEOD-71263 | biostudies-arrayexpress
Project description:The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages Macrophages derived from the C57BL/6 strain of mouse were challenged with increasing doses of LPS over a 24 hour time-course (0.5ng/ml, 5ng/ml, or 50ng/ml LPS). BALB/c derived macrophages were treated with any of 5ng/ml LPS, 10U/ml of recombinant mouse interferon-beta, or 10U/ml interferon-gamma, over a 24 hour timecourse. Sampling times were 0 hours (pre-treatment) and 1, 2, 4, 8, and 24 hours post-treatment in each case. 64 samples in total were analysed. These incorporated 6 different timecourse studies. A combination of statistical filtering using the Empirical Bayes function in Bioconductor package (R statistical software), and co-expression analysis using the network analysis tool BioLayout Express 3D, was used to compare the timecourse studies.
2014-03-24 | E-GEOD-44292 | biostudies-arrayexpress
Project description:Macrophages stimulated with lipopolysaccharide (LPS) plus interferon-g (IFNg) accumulate TGs in LDs, and long-chain acylcarnitines. Inhibition of TG synthesis results in diminished LD development, and increased long chain acylcarnitine levels, suggesting that FA fate is balanced between TG and acylcarnitine synthesis. Nevertheless, TG-synthesis is required for inflammatory macrophage function, since its inhibition negatively affects production of proinflammatory IL-1b, IL-6 and PGE2, and phagocytic capacity, and protects against LPS-induced sock in vivo.
2020-07-04 | GSE145523 | GEO
Project description:Macrophages play critical roles in inflammation and tissue homeostasis, and their functions are regulated by various autocrine, paracrine, and endocrine factors. We have previously shown that CTRP6, a secreted protein of the C1q family, targets both adipocytes and macrophages to promote obesity-linked inflammation in adipose tissue. However, the gene programs and signaling pathways directly regulated by CTRP6 in macrophage remain unknown. Here, we combine transcriptomic and phosphoproteomic analyses to show that CTRP6 activates inflammatory gene programs and signaling pathways in bone marrow-derived macrophages (BMDMs). Treatment of BMDMs with CTRP6 upregulates proinflammatory, and suppresses the anti-inflammatory, gene expression. We show that CTRP6 activates p44/42-MAPK, p38-MAPK, and NF-κB signalings to promote inflammatory cytokine secretion from BMDMs, and that pharmacologic inhibition of these signaling pathways largely abolish the effects of CTRP6. Pretreatment of BMDMs with CTRP6 further augments LPS-induced inflammatory signaling and cytokine secretion from BMDMs. Consistent with the metabolic phenotype of proinflammatory M1-like macrophages, CTRP6 treatment induces a shift toward aerobic glycolysis and lactate production, reduces oxidative metabolism, and elevates mitochondrial ROS production in BMDMs. We use a Ctrp6 knockout mouse model to further confirm the physiologic relevance of our in vitro findings. BMDMs from CTRP6-deficient mice are less inflammatory at baseline and show a marked suppression of LPS-induced inflammatory gene expression and cytokine secretion. Loss of CTRP6 in mice also dampens LPS-induced inflammation and hypothermia. Collectively, we provide mechanistic evidence that CTRP6 regulates macrophage function, and neutralizing CTRP6 activity may have beneficial effects in reducing inflammation.
2024-01-26 | PXD042268 | Pride
Project description:The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages Macrophages derived from the C57BL/6 strain of mouse were challenged with increasing doses of LPS over a 24 hour time-course (0.5ng/ml, 5ng/ml, or 50ng/ml LPS). BALB/c derived macrophages were treated with any of 5ng/ml LPS, 10U/ml of recombinant mouse interferon-beta, or 10U/ml interferon-gamma, over a 24 hour timecourse. Sampling times were 0 hours (pre-treatment) and 1, 2, 4, 8, and 24 hours post-treatment in each case.
2014-03-24 | GSE44292 | GEO
Project description:Long noncoding RNAs (lncRNAs) have emerged as novel regulators of macrophage biology and related inflammatory cardiovascular diseases. However, studies focused on lncRNAs in human macrophage subtypes, particularly human lncRNAs that are not conserved in rodents, are limited. Through RNA-seq of human monocyte-derived macrophages, we identified Suppressor of Inflammatory Macrophage Apoptosis lncRNA (SIMALR), a human macrophage-specific long intergenic noncoding RNA, to be highly induced in LPS/IFNγ-stimulated macrophages. Treatment of LPS/IFNγ stimulated THP1 human macrophages with SIMALR antisense oligonucleotides induced apoptosis of inflammatory macrophages, as shown by increased protein expression of cleaved PARP, caspase 9, caspase 3, and Annexin V+. RNA-seq of control versus SIMALR knockdown in LPS/IFNγ-stimulated human monocyte derived macrophages showed NTN1 to be significantly decreased upon SIMALR knockdown. As expected, NTN1 knockdown in LPS/IFNγ-stimulated macrophages induced apoptosis. This apoptotic phenotype was attenuated by adding recombinant NTN1 after SIMALR knockdown. Furthermore, NTN1 promoter-luciferase reporter activity was increased in HEK293T cells treated with lentiviral overexpression of SIMALR. NTN1 promoter activity is known to require HIF1α. RNA immunoprecipitation and microscopy studies suggest that SIMALR may interact with HIF1α to regulate NTN1 transcription, thereby regulating apoptosis of macrophages. In translational studies, SIMALR was found to be expressed in macrophages in human carotid atherosclerotic plaques of symptomatic patients. SIMALR is a non-conserved, human macrophage lincRNA expressed in human atherosclerosis that regulates macrophage apoptosis. SIMALR partners with HIF1α to regulate NTN1, which is a known macrophage survival factor. This work illustrates the importance of interrogating the functions of non-conserved human lincRNAs and exploring their translational and therapeutic potential in human atherosclerosis.
2022-11-23 | GSE212381 | GEO
Project description:Macrophages are a heterogeneous population of immune cells, which are critical for both the initiation and resolution of inflammation. Pro-inflammatory macrophages can be induced by the Th1 cytokine IFNγ and/or TLR triggers, like LPS. Here, we investigated the effects of IFNγ priming on LPS-induced gene expression in primary mouse macrophages.
2015-03-26 | GSE60290 | GEO
Project description: Not available
| S-EPMC4531482 | biostudies-literature