We have previously shown that rheumatoid factors (RF) produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a with remarkably low affinity. Nevertheless, B cells representative of this RF population proliferate vigorously in response IgG2a/chromatin immune complexes through a mechanism dependent on the sequential engagement of the BCR and Toll-like receptor 9 (TLR9). To more precisely address the role of both receptors in this response, we analyzed the signaling pathways activated in AM14 B cells stimulated with these complexes. We found that the BCR not only serves to direct the chromatin complex to an internal compartment where it can engage TLR9 but also transmits a suboptimal signal that in combination with the signals emanating from TLR9 leads to NF?B activation and proliferation. Importantly, engagement of both receptors leads to the upregulation of a group of gene products, not induced by the BCR or TLR9 alone, that include IL-2. These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process.
Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9.
No sample metadata fields
View SamplesHuman skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.
Specimen part, Disease, Disease stage
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesFour vehicle-treated and four HhAntag-treated pancreatic xenograft tumors were profiled for gene expression changes using Affymetrix U133 Plus 2.0 and Affymetrix Mouse Genome 430 2.0 arrays.
A paracrine requirement for hedgehog signalling in cancer.
No sample metadata fields
View SamplesAbout 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesHuman medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
No sample metadata fields
View SamplesBackground---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes.
Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects.
No sample metadata fields
View SamplesTo further understand the differences occurring in MCF10A cells as they polarize and differentiate in the Transwell model, we performed gene expression profiling with Affymetrix Human Genome U133 Plus 2.0 Arrays. Four experimental time points, were sampled: conventional cultures of MCF10A cells grown on plastic (Monolayer) and MCF10A cells plated on Transwells sampled at three TEER values, 200-300 cm2 (Base), 1400-1600 cm2 (Midpoint), and 3000-3200 cm2 (Plateau).
In vitro multipotent differentiation and barrier function of a human mammary epithelium.
No sample metadata fields
View SamplesIslet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse a model for human type 1 diabetes (T1DM). The molecular events leading to insulitis are poorly understood. Since TIDM is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease.
Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.
Age, Specimen part
View SamplesViral infections of the CNS are of increasing concern, especially among immunocompromised populations. Rodent models are often inappropriate for studies of CNS infection, as many viruses, including JC Virus (JCV) and HIV, cannot replicate in rodent cells. Consequently, human fetal brain-derived multipotential CNS progenitor cells (NPCs) that can be differentiated into neurons, oligodendrocytes, or astrocytes, have served as a model for CNS studies. NPCs can be non-productively infected by JCV, while infection of progenitor-derived astrocytes (PDAs) is robust. We profiled cellular gene expression at multiple times during differentiation of NPCs to PDAs. Several activated transcription factors show commonality between cells of the brain in which JCV replicates and lymphocytes in which JCV is likely latent. Bioinformatic analysis determined transcription factors that may influence the favorable transcriptional environment for JCV in PDAs. This study attempts to provide a framework for understanding the functional transcriptional profile necessary for productive JCV infection.
Differentiation of human fetal multipotential neural progenitor cells to astrocytes reveals susceptibility factors for JC virus.
Specimen part, Time
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