Leukemia inhibitory factor (LIF) is amongst the IL-6 family cytokines expressed in the lungs during pneumonia. However, the function of endogenous LIF during pneumonia has never been explored. The purpose of this study was to determine the transcriptional response to pneumonia in the lungs and whether or how this response is influenced by LIF.
Leukemia inhibitory factor signaling is required for lung protection during pneumonia.
Specimen part
View SamplesAlveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro. In vivo, we observed that Zcchc6 is expressed in mouse and human primary macrophages. Zcchc6-deficient mice are viable and born in Mendelian ratios and do not exhibit an observable spontaneous phenotype under basal conditions. Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation. Although loss of Zcchc6 also led to increased neutrophil emigration to the airways during pneumonia, these responses were not sufficient to impact host defense against infection.
The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
No sample metadata fields
View SamplesA growing body of evidence suggests that epithelial cells have special roles during pneumonia. The purpose of this study was to elucidate epithelial-specific responses during lung infection.
Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia.
Specimen part
View SamplesSchwann cell maturation is tightly controlled by a set of transcriptional regulators. We have deleted the zinc-finger transcription factor Sip1 specifically from immature Schwann cells and observed a dramatic developmental delay.
Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
View SamplesA common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of two transcription factors, STAT3 and NF-kappaB p65 (RelA), on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
View SamplesA common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of NF-kappaB RelA (p65) on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
View SamplesA common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of STAT3 on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
View SamplesCre-recombinase expression under control of an albumin promoter in the presence of floxed alleles is a highly effective and specific way to target gene mutations in hepatocytes. However, some concerns have been raised regarding off-target and/or toxic effects of cre itself, possibly confounding the interpretation of studies employing this approach. We have now used this tool to succesfully target gene deletions in hepatocytes during pneumonia, a condition which results in significant remodeling of the hepatic transcriptome. The goal of this study was to determine what effects, if any, cre expression alone has on hepatic gene expression during bacterial pneumonia.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
View SamplesThe aim of this study was to identify differentially-expressed genes in CCR4hi/CXCR3- and CCR4lo CXCR3+ CCR6+ human Th17 cell subsets
Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids.
No sample metadata fields
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