In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
No sample metadata fields
View SamplesSaliva (oral fluids) is an emerging biofluid poised for clinical diseases detection. Although the rationale for oral diseases applications (e.g. oral cancer) is clear, the rationale and relationship between systemic diseases and saliva biomarkers are unknown. In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Analysis of the transcriptomes in the mouse tumors, serum, salivary glands and saliva revealed that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in melanoma-bearing mice that can potentially be responsible for 82.6% of the up-regulated genes expression and 62.5% of the down-regulated gene expression in the mice saliva, respectively. We also confirmed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator that can induce expression of the transcription factor Egr-1 in the salivary gland. Taken together, our data support the conclusion that upon systemic disease development, a disease-specific change occurs in the salivary biomarker profile. Although the origins of the disease-specific salivary biomarkers are both systemic and local, stimulation of salivary gland by mediators released from remote tumors play an important role in regulating the salivary surrogate biomarker profiles.
Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.
No sample metadata fields
View SamplesA role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol.
All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Obesity accelerates epigenetic aging of human liver.
Sex, Age, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
View SamplesN=134 human liver samples from morbidly obese patients and healthy controls were analysed by array-based mRNA expression profiling. Liver messenger RNA expression datasets from the German patients were generated on the HuGene 1.1 ST gene array The purpose of the study was to correlate these gene expression data with body mass index and with an epigenetic measure of age acceleration based on DNA methylation data.
Obesity accelerates epigenetic aging of human liver.
Sex, Age, Disease, Subject
View SamplesImmunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND. METHODS: mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined.
Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning.
Age, Specimen part, Disease, Disease stage, Race
View SamplesGene expression data of primary and secondary glioblastoma subgroups.
No associated publication
No sample metadata fields
View SamplesDifferential gene expression profiling in peripheral blood mononuclear cells (PBMCs) was performed using Human Transcriptome Array 2 (HTA2)
No associated publication
Specimen part, Disease
View SamplesGestational diabetes mellitus (GDM) affects approximately 18% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 Beadchips) and expression (Affymetrix Transcriptome Microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
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