Unique Chemokine Profiles of Lung Tissue Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97835 | GEO | 2017/04/15
SECONDARY ACCESSION(S): PRJNA382989
REPOSITORIES: GEO
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2012-11-19 | E-GEOD-36331 | biostudies-arrayexpress
Project description:Neuropathic pain is a troublesome pathological condition without suitable treatments. In this study, we performed RNA sequencing (RNA-seq) analysis to reveal transcriptomic profiles of Anterior Cingulate Cortex (ACC) from chronic constriction injury (CCI) rats. We found 1628 differentially expressed genes (DEGs) were mainly involved in the inflammatory and immune process. Besides, cytokine signaling and other cell-defense related pathways mainly contribute to the occurrence and development of neuropathic pain. Then we classified the DEGs based on the time trend. Our results suggested that chemokines played a vital role in pain, and moreover, CCL5, CXCL9 and CXCL13, compared with CCL2, CCL3, CCL4, CCL6 and CCL7 had different time-dependent manners. In a word, targeting chemokines is of great significance to explore specific mechanisms and develop suitable drugs for neuropathic pain.
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Project description:Purpose: To investigate the effects of T cell-derived cytokines on gene and protein expression of chemokines in a human RPE cell line (ARPE-19). Methods: We used an in vitro co-culture system in which the RPE and CD3/28-activated T cells were separated by a membrane. Differential gene expression in the RPE cells of chemokine genes was quantified using three different microarrays. Protein expression was determined by single- and multiplex ELISA and immunoblotting. Results: Co-culture with activated T cells increased RPE mRNA and protein expression of chemokines CCL2 (MCP-1), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (MCP-2), CXCL1 (GRO-α), IL8 (CXCL8), CXCL9 (MIG), CXCL10 (IP10), CXCL11 (ITAC), and CX3CL1 (fractalkine). The secretion of CCL7 and CXCL9, 10, and 11 was polarized in the apical direction. Using recombinant human cytokines and neutralizing antibodies we identified IFNgamma and TNFalpha as the two major T cell-derived cytokines responsible for the RPE response. For CCL5, CXCL9, 10, 11, 16, and CX3CL1 we observed a synergistic effect of IFNgamma and TNFalpha in combination. CCL20, CXCL1 and 6, and IL8 were negatively regulated by IFNgamma. Conclusions: RPE cells responded to exposure to T cell-derived cytokines by upregulating expression of several chemokines related to microglial, T cell, and monocyte chemotaxis and activation. This inflammatory stress response may have implications for immune homeostasis in the retina, and for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration.
2012-11-19 | GSE36331 | GEO
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2009-08-17 | GSE8966 | GEO
Project description:We investigated the role of chemokines in regulating T-cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8+ T-cell infiltration in common solid tumors. T-cell infiltration required tumor cell-derived CCL5 and was amplified by IFN-dependent, myeloid cell-secreted CXCL9. Accordingly, CCL5-CXCL9 co-expression revealed immunoreactive tumors with prolonged survival and response to checkpoint blockade. Loss of CCL5 expression in human tumors was associated with epigenetic silencing through DNA methylation. Reduction of CCL5 expression caused TIL desertification whereas forced CCL5 expression prevented Cxcl9 and TIL loss and attenuated tumor growth in mice through IFN. The cooperation between tumor-derived CCL5 and IFN-inducible CXCR3 ligands secreted by myeloid cells is key for orchestrating T-cell infiltration in immunoreactive and immunoresponsive tumors.
2019-05-02 | GSE130571 | GEO
Project description:Infection of humans with Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, can cause hepatitis of varying severity. When the three human isolates of E. chaffeensis, each belongs to different geno-groups, are inoculated into severe combined immunodeficiency mice, the severity of clinical signs and bacterial burden detected in the liver are strain Wakulla>Liberty>Arkansas. Disseminated and granulomatous inflammation is evident in the liver of mice infected with strains Wakulla and Arkansas, respectively, but not in mice infected with strain Liberty. In this paper, we used microarray analysis to define transcriptional profiles characteristic to the histopathological features in the mouse liver. Cytokine and chemokine profiles were strikingly different among three strains of E. chaffeensis: IFN-γ, CCL5, CXCL1, CXCL2, CXCL7 and CXCL9 were highly up-regulated with strain Arkansas, TNF-α, CCL2, CCL3, CCL5, CCL6, CCL12, CCL20, CXCL2, CXCL7, CXCL9 and CXCL13 were highly up-regulated with strain Wakulla. With strain Liberty, only CXCL13 was highly up-regulated. In the livers infected with the Arkansas strain, monocytes/macrophages and NK cells were enriched in the granulomas and increase of NK cell-marker mRNAs was detected. Livers infected with the Wakulla strain displayed infiltration of significantly more neutrophils and increase of neutrophil-marker mRNAs. Genes up-regulated commonly in the liver infected with the three stains are other host innate immune and inflammatory response genes including several acute phase proteins. Genes down-regulated commonly are related to host physiologic functions. The results suggest that marked modulation of host cytokine and chemokine profiles by E. chaffeensis strains underlie the distinct host liver disease. Experiment Overall Design: E. chaffeensis strains Arkansas, Wakulla and Liberty were propagated in DH82 cells. Three to four week-old male ICR-scid mice were infected intraperitoneally with 10^6 E. chaffeensis-infected DH82 cells (typically >95% infected) containing approximately the same number of bacteria. At day 15 post infection (PI) mice were euthanized and livers were harvested. Experiment Overall Design: Total RNAs were extracted from E. chaffeensis-infected or mock-infected (uninfected) mouse liver. About 8 ug of each RNA sample was applied to double-strand cDNA preparation. The labeled cRNA was hybridized to GeneChip Mouse Genome 430 2.0 Array (Affymetrix). After washing and staining with streptoavidin phycoerythrin, the array was scanned. Experiment Overall Design: Three mice were examined for each of the 4 groups.
2009-08-22 | E-GEOD-8966 | biostudies-arrayexpress
Project description:Posttranscriptional regulation is emerging as a key factor in glucocorticoid (GC)-mediated gene regulation. We investigated the role of the human glucocorticoid receptor (GR) as an RNA-binding protein and its effect on mRNA turnover in human airway epithelial cells. Cell treatment with the potent GC budesonide accelerated the decay of CCL2 mRNA (t1/2=8±1 min vs. 62±17 min in DMSO-treated cells) and CCL7 mRNA (t1/2=15±4 min vs. 114±37 min), but not that of CCL5 mRNA (t1/2=231±8 min vs. 266±5 min) in the BEAS-2B cell line. This effect was inhibited by pre-incubation with an anti-GR antibody, indicating that GR itself plays a role in the turnover of these transcripts. Co-immunoprecipitation and biotin pulldown experiments showed that GR associates with CCL2 and CCL7 mRNAs, but not CCL5 mRNA. These methods confirmed CCL2 mRNA targeting by GR in human primary airway epithelial cells. Association of the GR was localized to the 5’UTR of CCL2 mRNA, and further mapped to nucleotides 44-60. The collection of transcripts associated with GR, identified by immunoprecipitation of GR-mRNA complexes followed by microarray analysis, revealed 479 transcripts that associated with GR. Computational analysis of the primary sequence and secondary structures of these transcripts yielded a GC-rich motif, which was shown to bind to GR in vitro. This motif was used to predict binding of GR to an additional 7889 transcripts. These results indicate that cytoplasmic GR interacts with a subset of mRNA through specific sequences and can regulate turnover rates, suggesting a novel posttranscriptional role for GR as an RNA-binding protein.
2011-06-24 | GSE24748 | GEO
Project description:Posttranscriptional regulation is emerging as a key factor in glucocorticoid (GC)-mediated gene regulation. We investigated the role of the human glucocorticoid receptor (GR) as an RNA-binding protein and its effect on mRNA turnover in human airway epithelial cells. Cell treatment with the potent GC budesonide accelerated the decay of CCL2 mRNA (t1/2=8±1 min vs. 62±17 min in DMSO-treated cells) and CCL7 mRNA (t1/2=15±4 min vs. 114±37 min), but not that of CCL5 mRNA (t1/2=231±8 min vs. 266±5 min) in the BEAS-2B cell line. This effect was inhibited by pre-incubation with an anti-GR antibody, indicating that GR itself plays a role in the turnover of these transcripts. Co-immunoprecipitation and biotin pulldown experiments showed that GR associates with CCL2 and CCL7 mRNAs, but not CCL5 mRNA. These methods confirmed CCL2 mRNA targeting by GR in human primary airway epithelial cells. Association of the GR was localized to the 5’UTR of CCL2 mRNA, and further mapped to nucleotides 44-60. The collection of transcripts associated with GR, identified by immunoprecipitation of GR-mRNA complexes followed by microarray analysis, revealed 479 transcripts that associated with GR. Computational analysis of the primary sequence and secondary structures of these transcripts yielded a GC-rich motif, which was shown to bind to GR in vitro. This motif was used to predict binding of GR to an additional 7889 transcripts. These results indicate that cytoplasmic GR interacts with a subset of mRNA through specific sequences and can regulate turnover rates, suggesting a novel posttranscriptional role for GR as an RNA-binding protein. The BEAS-2B cell line is derived from human tracheal epithelium transformed by an adenovirus 12-SV40 hybrid virus. For isolation of glucocorticoid receptor-associated transcripts, cytoplasmic lysates obtained from 1.6x107 cells/condition, 4 replicates per condition, were used to generate a collection of transcripts associated with GR by immunoprecipitation of the GR-mRNA complexes. The RNA from these IP's were extracted and labeled with the Illumina TotalPrep RNA Amplification Kit which generates biotin-labeled cRNA. This was hybridized to Illumina's Sentrix HumanRef-8,v3 Expression BeadChips. The data from 3 replicates of GR-IP and 4 replicates of Control-IP were used for global analysis of GR-mRNA interactions.
2011-06-24 | E-GEOD-24748 | biostudies-arrayexpress
Project description:Mouse aorta smooth muscle cells (SMCs) express TNF receptor superfamily member 1A (TNFR1) and lymphotoxin à receptor (LTÃR). Circumstantial evidence has linked the SMC LTÃR to tertiary lymphoid organogenesis in diseased aortae of hyperlipidemic mice. Here, we explored potential roles of TNFR1 and LTÃR activation in cultured SMCs. TNFR1 signaling by TNF activated the classical RelA NF-κB pathway, whereas LTÃR signaling by agonistic anti LTÃR antibody activated both the classical RelA and alternative RelB NF-κB pathways. Addition of both agonists synergized to enhance p100 inhibitor processing to the p52 subunit of NF-κB and promoted its nuclear translocation suggesting RelA-RelB cross-talk in transcription regulation. Correspondingly, microarrays showed that simultaneous TNFR1 and LTÃR activation when compared to activation of single receptors was followed by markedly elevated levels of mRNAs encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Furthermore, SMCs acquired prototypical features of mesenchymal cells known as lymphoid tissue organizers (LTOs), which control tertiary lymphoid organogenesis in autoimmune diseases, through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, VCAM-1, and ICAM-1. Experiments with ltbr-/- SMCs suggested that the LTÃR-RelB activation component of NF-κB signaling was obligatory to generate the LTO phenotype. TNFR1-LTÃR crosstalk also resulted in augmented synthesis and prolonged secretion of lymphorganogenic chemokine proteins into the culture medium. Thus, combined TNFR1-LTÃR signaling triggers SMC transdifferentiation into a phenotype that strikingly resembles LTOs. LTO-like SMCs may adopt a thus far unrecognized role in diseased arteries, i.e. to coordinate tertiary lymphoid organogenesis in atherosclerosis, aortic aneurysm, and transplant vasculopathy. Experiment Overall Design: Smooth muscle cells in tissue culture were stimulated with agonists and subsequently microarray, RT-PCR, and protein assays / analyses were performed
2009-12-02 | E-GEOD-15062 | biostudies-arrayexpress
Project description:Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1-2% of Americans. Its molecular pathogenesis remains poorly understood, and there are no FDA-approved treatments. We performed single cell RNA sequencing on blood and affected and unaffected skin from 7 LP patients. LP affected skin exhibited a robust immune infiltrate primarily composed of CD8 T-cells. These cells were specifically recruited by cytokines secreted by both superficial and dermal layers of skin. Basal keratinocytes and fibroblasts secrete CXCL9 and CXCL10, and fibroblasts secrete CCL19. Molecular analysis of LP skin and blood samples increased our understanding of disease pathogenesis and identified CCL19 as a new therapeutic target for treatment.
2024-10-03 | GSE254542 | GEO