Project description:Eicosanoids are potent regulators of gene expression of inflammatory cells. Pro- (leukotrienes B4 and C4) and anti-indflammatory (lipoxins A4 and B4) eicosanoids have been described in the literature but the detailed impact of these lipid mediators on the gene expression pattern of monocytic cells has not been studied in detail. We cultured the permanent monocytic cell line MonoMac 6 for 12 h in the absence (solvent control) and presence of these eicosanoids and quantified the differential gene expression patterns using the microarray technology. Keywords: comparative expression studies after eicosanoid stimulation
Project description:When macrophages encounter pathogens, they transiently induce an orchestrated cascade of pro- and anti-inflammatory genes. To obtain a precise picture of transcriptome-wide mRNA expression patterns, we performed RNA-Seq of total RNA at a high temporal resolution during the first two hours of macrophage activation. We systematically analyzed the contribution of translational regulation to the early phase of macrophage activation. While the expression of most cytokines is pre-dominanatly regulated by changes in mRNA levels, de-repression of translation was found to permit expression of many feedback inhibitors of the inflammatory response. Expression profiles of LPS-treated Raw264.7 cells (0, 15, 30, 45, 60, 75, 90 and 120 min after stimulation) were generated by deep sequencing using Illumina HiSeq 2000.
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.
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.
Project description:The hyperLOPIT proteomics platform combines mass-spectrometry with state-of-the-art machine learning for simultaneous “mapping” of the steady-state subcellular location of thousands of proteins. Here, we use a synergistic approach and combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate the spatio-temporal changes that occur during the pro-inflammatory response to lipopolysaccharide in the human monocytic leukaemia cell-line THP-1. We report cell-wide protein relocalisations upon LPS stimulation.
Project description:The cornerstone of mammalian intrinsic and innate immune defense against pathogens is the production of interferons (IFN), cytokines that stimulate anti-pathogen signaling pathways through the simultaneous expression of hundreds of interferon-stimulated genes (ISG). We compared the effects of IFN classes on the cellular proteome and relative restriction of virus progeny production across multiple physiologically relevant cell types and viruses. We integrated global proteome analyses with targeted mass spectrometry (MS), thermal proximity coaggregation-MS (TPCA-MS), and molecular virology assays to determine how ISGs differentially contribute to host antiviral capacities between immune-modulatory cell types. In differentiated macrophage-like monocytic cells, we classified sets of both shared and distinct ISG proteins responsive to each IFN class. We orthogonally confirmed the relative protein alterations using parallel reaction monitoring (PRM) by developing a proteotypic peptide library for ISG markers induced by each IFN class. Additional comparison to stimulation with pro-inflammatory LPS helped to contextualize the observed IFN signatures. We further assessed ISG protein interactions upon IFN types I and II stimulation, observing maintenance of key ISG protein complexes across treatments. Subsequent comparison of macrophage-like monocytic cells to primary keratinocytes enabled us to identify relative ISG abundances, cytokine induction, and antiviral capacities of both cell types across infections with several ubiquitous human viruses. Infections with herpes simplex virus-1 (HSV-1), adenovirus (AdV), and human cytomegalovirus (HCMV) revealed cell type-dependent differences in virus progeny production.
Project description:Analysis genes which alter after anti-dsDNA antibodies stimulation in human mesangial cells. The hypothesis is anti-dsDNA antibodies might affected a pro-inflammatory cytokine gene or genes in cell proliferation and apoptosis pathways
Project description:The objective of the study was to evaluate transcriptional response of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37. A functional genomics approach was used to establish a temporal transcriptional profile and identify differentially expressed genes in LPS (100ng/ml)-stimulated human monocytic THP-1 cells, in the presence or absence of LL-37 (20ug/ml) after 1, 2, 4 and 24 hrs of stimulation. The peptide significantly inhibited the expression of LPS-induced pro-inflammatory genes regulated by NF-kappa B, such as NF-kappa B1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappa B inhibitor, NF-kappa BIA, or genes involved in cell movement and recruitment (chemokines). The trends of gene expression were further validated by quantitative real-time PCR. This study implicates that LL-37 plays a role in the delicate balancing act of inflammatory responses.
Project description:Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently, anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. 1129 probe sets have been identified to be significantly up-regulated (p < 0.05) in LPS-treated cells when compared to controls. Text mining analysis of the top 50 LPS up-regulated genes revealed a functional connection in the NFκB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly down-regulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism, cell proliferation and transcriptional processes. Three genes were either related to NFκB transcription factor activity, cytokinesis or modulation of oxidative stress. In conclusion, our data provide evidence that Q10 down-regulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of pro-inflammatory mediators might be due to its impact on gene expression. Whole genome expression profiles were analysed from monocytes pre-incubated with ubiquinone (Q10) before subsequent stimulation with LPS. Stimulated (+LPS) and unstimulated (-LPS) monocytes were used as positive and negative controls, respectively. For every experimental group (3 groups in total), three Affymetrix Human Genome U133 Plus 2.0 arrays were used, thus resulting in the analysis of 9 microarrays.
Project description:Background: Identifying the immune components that are regulated by a2NTD, a peptide cleaved from the N-terminus of the a2 vacuolar ATPase. Methods: In this study, we used pathway-focused PCR arrays to determine the genes that are regulated in human monocytic cell line, THP-1 after a2NTD stimulation over time. Results: a2NTD up-regulated several cytokines including IL-1 alpha, IL-1 beta, and IL-10. Several chemokines were also upregulated including the MCP and MIP families. Conclusion: We believe a2NTD to be an immune modulator made by tumor cells that aid in preventing immune surveillance by up-regulating proteins in monocytes that are both pro-and anti-inflammatory in nature.