Homo sapiens
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PROVIDER: PRJNA106597 | ENA |
REPOSITORIES: ENA
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Project description:In sickle cell disease (SCD) hemoglobin S (HbS) polymerization renders red blood cells (RBC) both fragile and rigid and accounts for anemia and vasoocclusive crises (VOC). Abnormal RBC adhesion to vascular endothelial cells (VEC), in a context of chronic inflammation, cell activation and vascular tone abnormalities, is a major event in triggering VOC. Hydroxyurea (HU) is the only drug with a proven efficiency at decreasing VOC occurrence. HU decreases HbS polymerization and RBC adhesion. We studied HU effect on the other cellular partner of adhesion, i.e.VEC. HU-induced TrHBMEC transcriptome variations were analyzed by micro-arrays both in basal and pro-inflammatory conditions after 24h and 48h of treatment. Among the endothelial HU target genes we focused on those related to adhesion and inflammation phenomena. HU had no impact on adhesion genes as a whole, still expression of VCAM-1, a key adhesion receptor, was decreased. In contrast, HU had a significant effect on the inflammation gene cluster. It stimulates pro-inflammatory genes such as IL-1A, IL-1B, IL-6, IL-8, CCL2, CCL5 and CCL8 both at the mRNA and protein levels and also in HPMEC and HUVEC primary cells. This may suggest that HU increases inflammation in SCD patients to a threshold engaging an anti-inflammatory response. Keywords: Treated TrHBME cell line
2009-04-09 | GSE11372 | GEO
Project description:To analyze expression of inflammatory cytokines in Exhaled Breath Condensates from pediatric patients with sickle cell disease, asthma, sickle cell disease and asthma, and controls
2020-05-08 | GSE150056 | GEO
Project description:Baker2013 - Cytokine Mediated Inflammation in
Rheumatoid Arthritis
This model by Baker M. 2013, describes
the interaction between pro and anti-inflammatory cytokine
signalling in rheumatoid arthritis.
Using two ordinary differential equations, the first model
[BIOMD0000000550]
analyses bifurcation and describes different pathological states by
altering inflammatory regulation parameters.
The second model
[BIOMD0000000549]
includes the effect that ageing has on pro-inflammatory signalling,
allowing for time-dependant properties and disease progression to
be observed. The author also describes potential dosing for
reversal of the disease state.
This model is described in the article:
Mathematical modelling of
cytokine-mediated inflammation in rheumatoid arthritis.
Baker M, Denman-Johnson S, Brook BS,
Gaywood I, Owen MR.
Math Med Biol 2013 Dec; 30(4):
311-337
Abstract:
Rheumatoid arthritis (RA) is a chronic inflammatory disease
preferentially affecting the joints and leading, if untreated,
to progressive joint damage and disability. Cytokines, a group
of small inducible proteins, which act as intercellular
messengers, are key regulators of the inflammation that
characterizes RA. They can be classified into pro-inflammatory
and anti-inflammatory groups. Numerous cytokines have been
implicated in the regulation of RA with complex up and down
regulatory interactions. This paper considers a two-variable
model for the interactions between pro-inflammatory and
anti-inflammatory cytokines, and demonstrates that mathematical
modelling may be used to investigate the involvement of
cytokines in the disease process. The model displays a range of
possible behaviours, such as bistability and oscillations,
which are strongly reminiscent of the behaviour of RA e.g.
genetic susceptibility and remitting-relapsing disease. We also
show that the dose regimen as well as the dose level are
important factors in RA treatments.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000550.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000550 | BioModels
Project description:Baker2013 - Cytokine Mediated Inflammation in
Rheumatoid Arthritis - Age Dependant
This model by Baker M. 2013, describes
the interaction between pro and anti-inflammatory cytokine
signalling in rheumatoid arthritis.
Using two ordinary differential equations, the first model
[BIOMD0000000550]
analyses bifurcation and describes different pathological states by
altering inflammatory regulation parameters.
The second model
[BIOMD0000000549]
includes the effect that ageing has on pro-inflammatory signalling,
allowing for time-dependant properties and disease progression to
be observed. The author also describes potential dosing for
reversal of the disease state.
This model is described in the article:
Mathematical modelling of
cytokine-mediated inflammation in rheumatoid arthritis.
Baker M, Denman-Johnson S, Brook BS,
Gaywood I, Owen MR.
Math Med Biol 2013 Dec; 30(4):
311-337
Abstract:
Rheumatoid arthritis (RA) is a chronic inflammatory disease
preferentially affecting the joints and leading, if untreated,
to progressive joint damage and disability. Cytokines, a group
of small inducible proteins, which act as intercellular
messengers, are key regulators of the inflammation that
characterizes RA. They can be classified into pro-inflammatory
and anti-inflammatory groups. Numerous cytokines have been
implicated in the regulation of RA with complex up and down
regulatory interactions. This paper considers a two-variable
model for the interactions between pro-inflammatory and
anti-inflammatory cytokines, and demonstrates that mathematical
modelling may be used to investigate the involvement of
cytokines in the disease process. The model displays a range of
possible behaviours, such as bistability and oscillations,
which are strongly reminiscent of the behaviour of RA e.g.
genetic susceptibility and remitting-relapsing disease. We also
show that the dose regimen as well as the dose level are
important factors in RA treatments.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000549.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000549 | BioModels
Project description:<p>Sickle cell disease (SCD) is a severe debilitating hematological disorder associated with a high degree of morbidity and mortality. There are approximately 200,000 babies born with sickle cell disease each year, with the disease predominately affecting individuals in Africa. The overall global burden of the disease is tremendous, with more than 100,000 patients currently in the US and further millions worldwide. The governing bodies of the World Health Organization have recently adopted a resolution to strengthen the response to sickle disease in all affected countries and there is a definite need for high quality sickle cell disease research that has the potential to improve the treatment and prognosis of patients with this devastating disease. The clinical manifestations of SCD arise from a complex pathophysiology that includes hemolysis, acute vaso-occlusion, endothelial dysfunction, inflammation, and chronic organ damage. While the individual clinical course of this disease is highly variable, many of the associated complications demonstrate some degree of heritability. Intensive research into identifying genetic modifiers that can affect the pathophysiology of SCD has been limited to date and there is an urgent need to improve of our knowledge the molecular mechanisms underlying the clinical complications of SCD. The Sickle cell CIP project is investigating complication of stroke and pharmacogenomics of hydroxyurea response in patients with sickle cell anemia. The major benefit of hydroxyurea comes from its ability to induce fetal hemoglobin (HbF) and higher HbF levels are associated with reduced morbidity and mortality in SCA patients. We will perform whole exome and whole genome sequencing of SCA patients in order to identify genome variants associated with incidences of stroke and HbF response to hydroxyurea.</p>
| phs000691 | dbGaP
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea. CD71+ cells were isolated from whole blood of control individuals (n=2), pediatric patients without hydroxyurea treatment (n=3) and pediatric patients at hydroxyurea MTD (n=3). All 8 samples were analyzed for miRNA expression.
2011-11-21 | E-GEOD-32035 | biostudies-arrayexpress
Project description:Baker2017 - The role of cytokines, MMPs and
fibronectin fragments osteoarthritis
This model is described in the article:
Mathematical modelling of
cytokines, MMPs and fibronectin fragments in osteoarthritic
cartilage.
Baker M, Brook BS, Owen MR.
J Math Biol 2017 Feb; :
Abstract:
Osteoarthritis (OA) is a degenerative disease which causes
pain and stiffness in joints. OA progresses through excessive
degradation of joint cartilage, eventually leading to
significant joint degeneration and loss of function. Cytokines,
a group of cell signalling proteins, present in raised
concentrations in OA joints, can be classified into
pro-inflammatory and anti-inflammatory groups. They mediate
cartilage degradation through several mechanisms, primarily the
up-regulation of matrix metalloproteinases (MMPs), a group of
collagen-degrading enzymes. In this paper we show that the
interactions of cytokines within cartilage have a crucial role
to play in OA progression and treatment. We develop a
four-variable ordinary differential equation model for the
interactions between pro- and anti-inflammatory cytokines, MMPs
and fibronectin fragments (Fn-fs), a by-product of cartilage
degradation and up-regulator of cytokines. We show that the
model has four classes of dynamic behaviour: homoeostasis,
bistable inflammation, tristable inflammation and persistent
inflammation. We show that positive and negative feedbacks
controlling cytokine production rates can determine either a
pre-disposition to OA or initiation of OA. Further, we show
that manipulation of cytokine, MMP and Fn-fs levels can be used
to treat OA, but we suggest that multiple treatment targets may
be essential to halt or slow disease progression.
This model is hosted on
BioModels Database
and identified by:
MODEL1704120000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000928 | BioModels
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea.
2011-11-21 | GSE32035 | GEO
Project description:Endothelial cells play an essential role in inflammation through synthesis and secretion of chemoattractant cytokines and expression of adhesion molecules required for inflammatory cell attachment and infiltration. The mechanisms by which endothelial cells control its pro-inflammatory response depends on the type of inflammatory stimuli, endothelial cell origin and tissue involved. In the present study, we investigate the role of the transcription factor c-Myc in inflammation using a conditional knockout mouse model in which Myc is specifically deleted in the endothelium (EC-Myc KO). Using an experimental model of nonalcoholic steatohepatitis, we investigated the involvement of endothelial c-Myc in diet-induced inflammation. EC-Myc KO animals displayed enhanced pro-inflammatory response relative to control, which was characterized by increased expression of pro-inflammatory cytokines and leukocyte infiltration as well as worsened liver fibrosis. Transcriptome analysis suggested that different pro-inflammatory pathways are activated in control and endothelial Myc knockout after exposure to high-fat diet. Analysis of published single cell RNA-sequencing data available on human cirrhotic livers indicated that MYC was downregulated in endothelial cells relative to healthy individuals. Our results suggest a protective role for endothelial c-Myc in diet-induced liver inflammation and fibrosis. Targeting c-Myc and its downstream pathways in the endothelium may be a promising strategy for treatment of diet-induced inflammatory disease.
2022-06-30 | GSE176573 | GEO
Project description:Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability leading to microvascular obstruction and inflammation. While the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, where endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized “endothelialized” microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations of varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs leads to aberrant margination of the less-deformable RBC subpopulations towards the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (i.e., direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.
2024-08-08 | GSE274340 | GEO