MicroRNA miR-223 constrains lethal inflammation during Mycobacterium tuberculosis infection
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PROVIDER: PRJNA170123 | ENA |
REPOSITORIES: ENA
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Project description:The molecular mechanisms that control innate cell recruitment during chronic infection and inflammation, such as tuberculosis (TB), are incompletely understood. During TB, myeloid cells infiltrate the lung and sustain local inflammation. We identified microRNA (miR)-223 as one of the most abundant noncoding RNAs in lung parenchyma of TB patients and susceptible mice. MiR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation, by directly targeting the chemoattractants CXCL2, CCL3 and IL-6. Our study reveals an essential role for a single miR in TB. Moreover, we identify new targets for and assign novel biological functions to miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR223 is critical for control of TB and probably other nonresolving inflammatory diseases. MicroRNAs expression analysis in whole blood from 8 TB and 8 TST+ subjects. The samples were collected at Makerere University in Kampala, Uganda. Gene expression analysis of whole blood and lung tissue of C57/BL6 and miR-223-/- mouse strains (8-12 weeks of age) after Mtb aerosol infection. Samples were collected at 7, 14 and 21 days post infection.
2014-04-21 | E-GEOD-39163 | biostudies-arrayexpress
Project description:The molecular mechanisms that control innate cell recruitment during chronic infection and inflammation, such as tuberculosis (TB), are incompletely understood. During TB, myeloid cells infiltrate the lung and sustain local inflammation. We identified microRNA (miR)-223 as one of the most abundant noncoding RNAs in lung parenchyma of TB patients and susceptible mice. MiR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation, by directly targeting the chemoattractants CXCL2, CCL3 and IL-6. Our study reveals an essential role for a single miR in TB. Moreover, we identify new targets for and assign novel biological functions to miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR223 is critical for control of TB and probably other nonresolving inflammatory diseases.
2014-04-21 | GSE39163 | GEO
Project description:MicroRNA-223, a principal myeloid-specific anti-inflammatory microRNA, is dysregulated in numerous inflammatory conditions and cancers. We found that miR-223 deficient zebrafish displayed augmented neutrophilic inflammation, which was due primarily to elevated activation of the canonical NF-B pathway. To our surprise, the NF-B over-activation was restricted to the basal epithelial cells, a squamous layer permeable to oxygen and chemicals. MiR-223 was expressed in epithelial cells and directly down-regulated multiple components in the NF-B signaling pathway in zebrafish and human. Both phagocytic and epithelial miR-223 suppressed neutrophil wound response and NF-B activation in the basal epithelial cells. Together, our data provide the mechanism of the multifaceted role of miR-223 and highlight the previously overlooked relevance of epithelial cells in miR-223 related diseases.
2017-02-17 | GSE94996 | GEO
Project description:We used a multi-omics approach combining transcriptomics, proteomics and metabolomics to study the impact of over-expression and inhibition of the microRNA miR-223, a pleiotropic regulator of metabolic-related disease, in the RAW monocyte-macrophage cell line. We analyzed the levels of proteins, mRNAs, and metabolites in order to identify genes involved in miR-223 regulation, to determine candidate disease biomarkers and potential therapeutic targets. We observed that both up- and down-regulation of miR-223 induced profound changes in the mRNA, protein and metabolite profiles in RAW cells. Microarray-based transcriptomics evidenced a change in 120 genes that were linked predominantly to histone acetylation, bone remodeling and RNA regulation. In addition, 30 out the 120 genes encoded long noncoding RNAs. The nanoLC-MS/MS revealed that 52 proteins were significantly altered when comparing scramble, pre- and anti-miR-223 treatments. Sixteen out of the mRNAs coding these proteins genes are predicted to have binding sites for miR-223. CARM-1, Ube2g2, Cactin and Ndufaf4 were confirmed to be miR-223 targets by western blotting. Analyses using Gene Ontology annotations evidenced association with cell death, splicing and stability of mRNAs, bone remodeling and cell metabolism. miR-223 alteration changed the expression of CARM-1, Ube2g2, Cactin and Ndufaf4 during osteoclastogenesis and macrophage, indicating that these genes are potential biomarkers of these processes. The most important discriminant metabolites found in the metabolomics study were found to be hydrophilic amino acids, carboxylic acids linked to metabolism and pyrimidine nucleotides, indicating that changes in miR-223 expression alter the metabolic profile of cells, and may affect their apoptotic and proliferative state.
2021-03-29 | PXD009844 | Pride
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis.
2013-02-07 | GSE44120 | GEO
Project description:Gene expression profiling of bone marrow derived eosinophils from miR-223 wildtype or miR-223 deficient mice
2012-08-25 | E-MEXP-3350 | biostudies-arrayexpress
Project description:Background: Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that recently have been found in the blood to be relevant as disease biomarkers. Objective: We aimed to explore miRNAs potential as blood biomarkers for psoriasis. Methods: Using microarray and quantitative real-time PCR we measured the global miRNA expression in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and healthy controls. Results: We identified several deregulated miRNAs in the blood from patients with psoriasis including miR-223 and miR-143 which were found to be significantly upregulated in the PBMCs from patients with psoriasis compared with healthy controls (FCH=1.63, P<0.01; FCH=2.18, P<0.01, respectively). In addition, miR-223 and miR-143 significantly correlated with the PASI score (r = 0.46, P<0.05; r=0.55, P<0.02, respectively). Receiver-operating characteristic analysis (ROC) showed that miR-223 and -143 have the potential to distinguish between psoriasis and healthy controls (miR-223: Area under the curve (AUC) = 0.80, miR-143: AUC = 0.75). Interestingly, after 3-5 weeks of treatment with methotrexate following a significant decrease in psoriasis severity, miR-223 and miR-143 were significantly downregulated in the PBMCs from patients with psoriasis. Conclusion: We suggest that changes in the miR-223 and miR-143 expressions in PBMCs from patients with psoriasis may serve as novel biomarkers for disease activity in psoriasis; however, further investigations are warranted to clarify their specific roles.
2014-06-10 | GSE55515 | GEO
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis. miR-223 was transfected in OE33 cells using 10nM pre-miR hsa-miR-223 miRNA precursor (Ambion, Life Technologies, Grand Island, NY) and lipofectamin 2000 (OE33_223_1 and OE33_223_2). Mock control OE33 cells were transfected with a negative control pre-miR miRNA (OE33_NEG_1 and OE33_NEG_2). HumanHT-12 v4 Expression BeadChip arrays (Illumina, San Diego, CA) were used for microarray hybridizations to examine the global gene expression of two biological replicated experiments (four samples in total). The array targets more than 25,000 annotated genes with 47,323 unique probes derived from the National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) Release 38 and UniGene (Build 199) databases.
2013-02-07 | E-GEOD-44120 | biostudies-arrayexpress
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 are emergent highly pathogenic human respiratory viruses causing acute lethal disease associated with lung damage and dysregulated inflammatory responses. SARS-CoV envelope protein (E) is a virulence factor involved in the activation of various inflammatory pathways. Here, we study the contribution of host miRNAs to the virulence mediated by E protein. Small RNAseq analysis of infected mouse lungs identified miRNA-223 as a potential regulator of pulmonary inflammation, since it was significantly increased in SARS-CoV-WT virulent infection as compared to the attenuated SARS-CoV-∆E infection. In vivo inhibition of miRNA-223-3p increased mRNA levels of pro-inflammatory cytokines and NLRP3 inflammasome, suggesting that during lung infection, miRNA-223 might contribute to restrict an excessive inflammatory response. Interestingly, miRNA-223-3p inhibition also increased the levels of the CFTR transporter, which is involved in edema resolution and was significantly downregulated in the lungs of mice infected with the virulent SARS-CoV-WT virus. At the histopathological level, a decrease in the pulmonary edema was observed when miR-223-3p was inhibited, suggesting that miRNA-223-3p was involved in the regulation of the SARS-CoV-induced inflammatory pathology. These results indicate that miRNA-223 participates in the regulation of E protein mediated- inflammatory response during SARS-CoV infection by targeting different host mRNAs involved in the pulmonary inflammation and identify miRNA-223 as a potential therapeutic target in SARS-CoV infection.
2022-02-04 | GSE180563 | GEO
Project description:Neuropeptide CGRP limits ILC2 responses and constrains type 2 inflammation
| PRJNA545529 | ENA