Blood lymphocytes of autoimmune disease patients receiving FK506 exhibit normal ex vivo cytokine gene expression and proliferative responses

1993 ◽  
Vol 38 (3) ◽  
pp. 179-183 ◽  
Author(s):  
Bonnie Lemster ◽  
Jacky Woo ◽  
Angus W. Thomson
2004 ◽  
Vol 172 (4) ◽  
pp. 2687-2696 ◽  
Author(s):  
Annette Audigé ◽  
Erika Schlaepfer ◽  
Athos Bonanomi ◽  
Helene Joller ◽  
Marlyse C. Knuchel ◽  
...  

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Sylwia Wasiak ◽  
Kim E. Dzobo ◽  
Brooke D. Rakai ◽  
Yannick Kaiser ◽  
Miranda Versloot ◽  
...  

Abstract Background Patients with cardiovascular disease (CVD) and type 2 diabetes (DM2) have a high residual risk for experiencing a major adverse cardiac event. Dysregulation of epigenetic mechanisms of gene transcription in innate immune cells contributes to CVD development but is currently not targeted by therapies. Apabetalone (RVX-208) is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins—histone acetylation readers that drive pro-inflammatory and pro-atherosclerotic gene transcription. Here, we assess the impact of apabetalone on ex vivo inflammatory responses of monocytes from DM2 + CVD patients. Results Monocytes isolated from DM2 + CVD patients and matched controls were treated ex vivo with apabetalone, interferon γ (IFNγ), IFNγ + apabetalone or vehicle and phenotyped for gene expression and protein secretion. Unstimulated DM2 + CVD monocytes had higher baseline IL-1α, IL-1β and IL-8 cytokine gene expression and Toll-like receptor (TLR) 2 surface abundance than control monocytes, indicating pro-inflammatory activation. Further, DM2 + CVD monocytes were hyper-responsive to stimulation with IFNγ, upregulating genes within cytokine and NF-κB pathways > 30% more than control monocytes (p < 0.05). Ex vivo apabetalone treatment countered cytokine secretion by DM2 + CVD monocytes at baseline (GROα and IL-8) and during IFNγ stimulation (IL-1β and TNFα). Apabetalone abolished pro-inflammatory hyper-activation by reducing TLR and cytokine gene signatures more robustly in DM2 + CVD versus control monocytes. Conclusions Monocytes isolated from DM2 + CVD patients receiving standard of care therapies are in a hyper-inflammatory state and hyperactive upon IFNγ stimulation. Apabetalone treatment diminishes this pro-inflammatory phenotype, providing mechanistic insight into how BET protein inhibition may reduce CVD risk in DM2 patients.


Immunology ◽  
1998 ◽  
Vol 95 (2) ◽  
pp. 242-247 ◽  
Author(s):  
WICHER ◽  
SCAROZZA ◽  
RAMSINGH ◽  
WICHER

2009 ◽  
Vol 50 (3) ◽  
pp. 322 ◽  
Author(s):  
Choong-Gu Lee ◽  
Anupama Sahoo ◽  
Sin-Hyeog Im

2015 ◽  
Vol 23 (3) ◽  
pp. 617-626 ◽  
Author(s):  
Nophar Geifman ◽  
Sanchita Bhattacharya ◽  
Atul J Butte

Abstract Objective Cytokines play a central role in both health and disease, modulating immune responses and acting as diagnostic markers and therapeutic targets. This work takes a systems-level approach for integration and examination of immune patterns, such as cytokine gene expression with information from biomedical literature, and applies it in the context of disease, with the objective of identifying potentially useful relationships and areas for future research. Results We present herein the integration and analysis of immune-related knowledge, namely, information derived from biomedical literature and gene expression arrays. Cytokine-disease associations were captured from over 2.4 million PubMed records, in the form of Medical Subject Headings descriptor co-occurrences, as well as from gene expression arrays. Clustering of cytokine-disease co-occurrences from biomedical literature is shown to reflect current medical knowledge as well as potentially novel relationships between diseases. A correlation analysis of cytokine gene expression in a variety of diseases revealed compelling relationships. Finally, a novel analysis comparing cytokine gene expression in different diseases to parallel associations captured from the biomedical literature was used to examine which associations are interesting for further investigation. Discussion We demonstrate the usefulness of capturing Medical Subject Headings descriptor co-occurrences from biomedical publications in the generation of valid and potentially useful hypotheses. Furthermore, integrating and comparing descriptor co-occurrences with gene expression data was shown to be useful in detecting new, potentially fruitful, and unaddressed areas of research. Conclusion Using integrated large-scale data captured from the scientific literature and experimental data, a better understanding of the immune mechanisms underlying disease can be achieved and applied to research.


1994 ◽  
Vol 68 (6) ◽  
pp. 293-298 ◽  
Author(s):  
F. H. M. Cluitmans ◽  
B. H. J. Esendam ◽  
J. E. Landegent ◽  
R. Willemze ◽  
J. H. F. Falkenburg

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