We recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the carbon monoxide releasing molecule, CORM-2. The E. coli microarray analysis shows that E. coli CORM-2 response is multifaceted with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in posttranslational modification, such as chaperones. CORM-2 has higher impact in E. coli cells grown anaerobically, as judged by the existence of repressed genes belonging to eight functional classes which are absent in aerobically CORM-2 treated cells. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.
Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
No sample metadata fields
View SamplesPattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-) and IL-1 are proinflammatory cytokines which can be essential for resistance against infection, but if produced at high levels, may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine which dampens proinflammatory responses, but can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. Here, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF- and IL-1, but high levels of IL-10 in response to TLR4 and TLR2 ligands LPS and PamCSK4, and Burkholderia pseudomallei a Gram-negative bacterium which activates TLR 2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN dependent, but IL-27 independent mechanism. Further, type I IFN contributed to differential IL-1 and IL-12 production in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages, via both IL-10-dependent and independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.
Differential Production of Type I IFN Determines the Reciprocal Levels of IL-10 and Proinflammatory Cytokines Produced by C57BL/6 and BALB/c Macrophages.
Sex, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesAnalysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 2]
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesAnalysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 1]
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
Sex, Specimen part
View SamplesCharacterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
No sample metadata fields
View SamplesCharacterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.
No sample metadata fields
View SamplesAnalysis of synchronized HCT116 cells at various time points up to 10 hours following treatment with DMSO or Nocodazole.
A signature-based method for indexing cell cycle phase distribution from microarray profiles.
Cell line, Treatment
View SamplesRNA sequencing was performed on uninjured, and injured (FSP1, and aSMA expressing) fibroblasts from mice hearts. Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis as well as physiological repair, making them a difficult therapeutic target. Fibroblasts are a heterogeneous cell population lacking unique functional classification. We demonstrated that FSP1 and aSMA expressing cells are distinct, post-injury fibroblasts in the heart, kidney, and skin and exhibit unique temporal expression patterns. Using mice that express GFP under the FSP1 or aSMA promoters, we isolated these fibroblasts from mouse hearts after myocardial infarction. Protein and transcript arrays, cellular assays as well as in vivo granulation tissue formation were used to determine their functional role(s) in healing and fibrosis. Whereas aSMA+ fibroblasts predominated in producing matrix proteins, FSP1+ fibroblasts significantly promoted angiogenesis. These studies have the potential to shift our focus towards viewing fibroblasts not only molecularly but also as functionally heterogeneous and provide a new paradigm with which to approach treatment for organ fibrosis. Overall design: Fibroblasts were isolated from uninjured BL6 mice for control. FSP1 and aSMA expressing fibroblasts were isolated from transgenic mice that express GFP under FSP1 or aSMA promoter. GFP positive cells were freshly sorted 10 days following myocardial infarction from mice ventricles. RNA was prepared using Ambion RNAqueous kit and submitted for RNA sequencing.
Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing.
Age, Specimen part, Subject
View Samples