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GSE74145
Rattus norvegicus
8 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting programming effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes.
Publication Title
Intermittent neonatal hypoxia elicits the upregulation of inflammatory-related genes in adult male rats through long-lasting programming effects.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we apply this approach to inflammatory bowel disease by examining groups of Crohn's disease (CD) and ulcerative colitus (UC) patients. The induced plasma induced signatures are compared to those of Type 1 diabetes patients (RO T1D) as well as unrelated healthy controls (uHC).
Publication Title
Plasma-induced signatures reveal an extracellular milieu possessing an immunoregulatory bias in treatment-naive paediatric inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inflammation is common to many disorders and responsible for tissue and organ damage. However, the associated peripheral cytokine milieu is frequently dilute and difficult to measure, necessitating development of more sensitive and informative biomarkers for mechanistic studies, earlier diagnosis, and monitoring therapeutic interventions. Previously, we have shown that sera from type 1 diabetes (T1D) patients induces a unique disease-specific pro-inflammatory transcriptional profile in fresh peripheral blood mononuclear cells (PBMCs) compared to sera of healthy controls.
Publication Title
Use of transcriptional signatures induced in lymphoid and myeloid cell lines as an inflammatory biomarker in Type 1 diabetes.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens, Rattus norvegicus
- 39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells (PBMCs) drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens.
Publication Title
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens.
Publication Title
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 53 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Human type 1 diabetes (T1D) arises through autoimmunity towards the insulin-producing pancreatic cells and is modeled by the BioBreeding (BB) rat. Factors associated with islet autoimmunity are dilute and difficult to directly measure in the periphery. Therefore, we previously utilized microarray-based bioassay where human T1D sera were used to induce a disease-specific gene expression signature in unrelated, healthy peripheral blood mononuclear cells (PBMC).
Publication Title
Identification of a serum-induced transcriptional signature associated with type 1 diabetes in the BioBreeding rat.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The incidence of Type 1 diabetes (T1D), a T-cell mediated autoimmunity that targets the insulin secreting -cells, has significantly increased, suggesting greater environmental pressure. In studies of T1D families and the BioBreeding rat model, we have identified a peripheral innate inflammatory state that is associated with diabetes susceptibility, consistent with pattern recognition receptor (PRR) ligation, but independent of disease progression. Here, compared to control strains, islets of spontaneously diabetic BB DRlyp/lyp and nondiatetic BB DR+/+ weanlings provided a standard cereal diet were found to temporally express a proinflammatory transcriptional program consistent with microbial antigen exposure that included numerous cytokines/chemokines. Dependence of this proinflammatory phenotype on the diet and gastrointestinal microbiota was investigated by transitioning DR+/+ weanlings to a hydrolyzed casein diet (HCD) or treating them with antibiotics to respectively alter or reduce PRR ligand exposure.
Publication Title
Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 275 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples.
Publication Title
Molecular signatures differentiate immune states in type 1 diabetic families.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Like humans, the NOD mouse and other diabetes susceptible rat strains, T1D in BB rats is dependent on the major histocompatibility complex (MHC, insulin dependent diabetes mellitus locus 1, Iddm1) located on chromosome 20. In rats this is the HLA-DQB1 homologue RT1-B, specifically the RT1u haplotype. Our studies employ congenic derivatives of the BB rat, the DRlyp/lyp and DR+/+ strains, which differ only by the 2 Mb lyp (lymphopenia, Iddm2) region on chromosome 4. TID in the lymphopenic DRlyp/lyp rat is spontaneous and onset occurs in 100% of animals during adolescence (65.3+/-6.3 days) due to a recessive mutation within GIMAP5 (GTPase, IMAP family member 5). Gimap5 is a mitochondrial GTP-binding protein necessary for post-thymic T cell survival. The spontaneously diabetic phenotype observed in DRlyp/lyp rats is thought to be elicited through deficiency in CD4+CD25+ TREG cells as T1D in lymphopenic BB rats can be rescued through adoptive transfer of this population. Genetic variation in GIMAP5 has been associated with the development of protein-tyrosine phosphatase-2 (IA-2) autoantibodies in human T1D [28] and is significantly associated with systemic lupus erythematosus (SLE). The non-lymphopenic DR+/+ strain possesses wild-type GIMAP5 alleles and does not develop spontaneous T1D, however, T1D is inducible through administration of lymphotoxic anti-RT6 monoclonal antibody and immune activating polyinosinic polycytidylic acid (poly I:C; a ligand of toll-like receptor 3), or through viral depletion of CD4+CD25+ regulatory T (TREG) cells. Such treatments do not induce T1D in the related Wistar-Furth (WF) rats and suggest the presence of an underlying diabetic predisposition in BB rats that is phenotypically manifested upon loss of immune regulation.
Publication Title
Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes.
Sample Metadata Fields
Age, Specimen part
View Samples