Buprenorphine induces human fetal membrane sterile inflammation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1190073 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Opioid-use disorder (OUD) during pregnancy has increased in the United States to critical levels and is a leading cause of maternal morbidity and mortality. Untreated OUD is associated with pregnancy complications in particular, preterm birth. Medications for OUD, such as buprenorphine, are recommended with the added benefit that treatment during pregnancy increases treatment post-partum. However, the rate of preterm birth in individuals using illicit opioids or being treated with opioid agonist therapeutics is double that of the general population. Since inflammation in the placenta and fetal membranes (FM) is a common underlying cause of preterm birth, we sought to determine if the opioid, buprenorphine, induces sterile inflammation in human FMs and to examine the mechanisms involved. Using an established in vitro human FM explant system, we report that buprenorphine significantly increased FM secretion of the inflammatory cytokine IL-6; the neutrophilic chemokine IL-8; and the inflammasome-mediated cytokine IL-1b, mirroring the inflammatory profile commonly seen at the maternal-fetal interface in preterm birth. Other factors that were elevated in FMs exposed to buprenorphine included the mediators of membrane weakening, prostaglandin E2 (PGE2), and the matrix metalloproteinases, MMP1 and MMP9. Furthermore, this sterile inflammatory and weakening FM response induced by buprenorphine was mediated in part by innate immune Toll-like receptor 4 (TLR4), the NLRP3 inflammasome, the m-opioid receptor, and downstream NFkB and ERK/JNK/MAPK signaling. This may provide the mechanistic link between opioid use in pregnancy and the elevated risk for preterm birth. Since there are adverse consequences of not treating OUD, our findings may help identify ways to mitigate the impact opioids have on pregnancy outcomes while allowing the continuation of maintenance therapy.
2025-02-07 | GSE282727 | GEO
Project description:Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, have been recently linked to tissue protection and repair. Their role, especially in sterile lung injury, is unknown. Using single cell RNA sequencing (scRNA-seq), spectral analysis and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and induces an accompanying tissue repair programme, associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1), limiting tissue damage in a DNGR-1 dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defence against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.
2025-02-04 | GSE270623 | GEO
Project description:Sterile stimuli can trigger inflammatory responses, and in some cases can lead to a variety of acute or chronic diseases. In this study, we hypothesize that a benzimidazole inhibitor may be used as a therapeutic in the treatment of sterile inflammation. In vitro, this inhibitor blocks TLR signalling and inflammatory responses. The benzimidazole inhibitor does not prevent mouse macrophage activation after stimulation with 2, 6, 10, 14-tetramethylpentadecane (TMPD, also known as pristane), a hydrocarbon oil that mimics features of sterile inflammation when injected in vivo. However, C57BL/6 female mice treated with the benzimidazole inhibitor exhibited a significant reduction of pristane-dependent induction of splenocyte number and weight. Conversely, no significant difference was observed in males. Using mass spectrometry, we found that the urine of pristane-injected mice contained increased levels of putative markers for several inflammatory diseases, which were reduced by the benzimidazole inhibitor. To study the mechanism, we showed that pristane-injected mice had increased cell free DNA in serum, which was not impacted by inhibitor treatment. However, chemokine release (e.g. MCP-1, RANTES and TARC) was significantly reduced in inhibitor-treated mice. Thus, the benzimidazole inhibitor might be used as a new drug to block the recruitment of immune cells during sterile inflammatory diseases in humans.
2020-07-27 | PXD017492 | Pride
Project description:Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, have been recently linked to tissue protection and repair. Their role, especially in sterile lung injury, is unknown. Using single cell RNA sequencing (scRNA-seq), spectral analysis and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and induces an accompanying tissue repair programme, associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1), limiting tissue damage in a DNGR-1 dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defence against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.
2025-02-04 | GSE270725 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE10057: The Epstein-Barr Virus latent membrane protein 1 (LMP1) induces cellular microRNA146a GSE10105: Alteration of microRNA gene expression by EBV encoded LMP1 oncogene Keywords: SuperSeries Refer to individual Series
2008-01-08 | E-GEOD-10107 | biostudies-arrayexpress
Project description:Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, have been recently linked to tissue protection and repair. Their role, especially in sterile lung injury, is unknown. Using single cell RNA sequencing (scRNA-seq), spectral analysis and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and induces an accompanying tissue repair programme, associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1), limiting tissue damage in a DNGR-1 dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defence against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.
2025-02-04 | GSE270870 | GEO
Project description:Inflammation is implicated in the onset and progression of various diseases, including cerebral pathologies. Here, we report that DJ-1, which plays a role within cells as an antioxidant protein, functions as a damage-associated molecular pattern (DAMP) and triggers inflammation if released from dead cells into the extracellular space. We first found that recombinant DJ-1 protein induces the production of various inflammatory cytokines in bone marrow-derived macrophages (BMMs) and dendritic cells (BMDCs). We further identified a unique peptide sequence in the αG and αH helices of DJ-1 that activates Toll-like receptor 2 (TLR2) and TLR4. In the ischemic brain, DJ-1 is released into the extracellular space from necrotic neurons within 24 h after stroke onset and makes direct contact with TLR2 and TLR4 in infiltrating myeloid cells. Although DJ-1 deficiency in a murine model of middle cerebral artery occlusion did not attenuate neuronal injury, the inflammatory cytokine expression in infiltrating immune cells was significantly decreased. Next, we found that the administration of an antibody to neutralize extracellular DJ-1 suppressed cerebral post-ischemic inflammation and attenuated ischemic neuronal damage. Our results demonstrate a previously unknown function of DJ-1 as a DAMP and suggest that extracellular DJ-1 could be a therapeutic target to prevent inflammation in tissue injuries and neurodegenerative diseases.
| S-EPMC8136727 | biostudies-literature
Project description:LncRNA and transcriptomic analysis of fetal membrane revealed potential targets involved in oligohydramnios
| PRJNA598035 | ENA
Project description:The purpose of our study was to characterize methylomic status by comparing the zone of fetal membranes (site of rupture (ZAM) and away from the site (ZIM)) and the tissue layer (amnion and choriodecidua). Nine fetal membranes were collected by cesarean section at term before labor. . After classifying genes in specific biological processes, we highlight particular patterns like inflammation.
2022-02-03 | E-MTAB-10520 | biostudies-arrayexpress
Project description:Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kγ) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is still a matter of discussion. Here we show that PI3Kγ is required for immune responses in which TLR9 is a relevant trigger. We demonstrate the requirement of PI3Kγ for TLR9-induced inflammation in a model of CpG-induced pleurisy. Such requirement was further observed in inflammatory models where DNA sensing via TLR9 contributes to disease, such as silicosis and drug-induced liver injury. Using adoptive transfer, we demonstrate that PI3Kγ is important not only in leukocytes but also in parenchymal cells for the progression of inflammation. We demonstrate this crosstalk between TLR9 and PI3Kγ in vitro using human PBMCs. The inhibition of PI3Kγ in CpG-stimulated PBMCs resulted in reduction of both cytokine production and phosphorylated Akt. Therefore, drugs that target PI3Kγ have the potential to treat diseases mediated by excessive TLR9 signalling.
| S-EPMC6910931 | biostudies-literature