The early transcriptomic response to interleukin 1β and interleukin 33 in rat neonatal cardiomyocytes

Barrett, Oliver; Yndestad, Arne; Marshall, Andrew K.; Sugden, Peter H.; Clerk, Angela

doi:10.1016/j.cyto.2012.11.004

Cited by 2 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…) and following interleukin 1β and interleukin 33 stimulation (Barrett et al. ). Relevant to the decrease in COX2 transcript expression noted after p38MAPK inhibition with BIRB796 in the current study, inhibition of the MAPK‐activated protein kinase 2 (MK2) decreases COX2 protein synthesis without affecting mRNA levels (Streicher et al.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases

Yuan

et al. 2013

Physiol Rep

View full text Add to dashboard Cite

Engineered cardiac tissues (ECTs) are platforms to investigate cardiomyocyte maturation and functional integration, the feasibility of generating tissues for cardiac repair, and as models for pharmacology and toxicology bioassays. ECTs rapidly mature in vitro to acquire the features of functional cardiac muscle and respond to mechanical load with increased proliferation and maturation. ECTs are now being investigated as platforms for in vitro models for human diseases and for pharmacologic screening for drug toxicities. We tested the hypothesis that global ECT gene expression patterns are complex and sensitive to mechanical loading and tyrosine kinase inhibitors similar to the maturing myocardium. We generated ECTs from day 14.5 rat embryo ventricular cells, as previously published, and then conditioned constructs after 5 days in culture for 48 h with mechanical stretch (5%, 0.5 Hz) and/or the p38 MAPK (p38 mitogen-activated protein kinase) inhibitor BIRB796. RNA was isolated from individual ECTs and assayed using a standard Agilent rat 4 × 44k V3 microarray and Pathway Analysis software for transcript expression fold changes and changes in regulatory molecules and networks. Changes in expression were confirmed by quantitative-polymerase chain reaction (q-PCR) for selected regulatory molecules. At the threshold of a 1.5-fold change in expression, stretch altered 1559 transcripts, versus 1411 for BIRB796, and 1846 for stretch plus BIRB796. As anticipated, top pathways altered in response to these stimuli include cellular development, cellular growth and proliferation; tissue development; cell death, cell signaling, and small molecule biochemistry as well as numerous other pathways. Thus, ECTs display a broad spectrum of altered gene expression in response to mechanical load and/or tyrosine kinase inhibition, reflecting a complex regulation of proliferation, differentiation, and architectural alignment of cardiomyocytes and noncardiomyocytes within ECT.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases

Yuan

et al. 2013

Physiol Rep

View full text Add to dashboard Cite

show abstract

“…Interestingly, interleukin-11 is another cytokine related to cardioprotection [253,254] and, along with interleukin-6 and interleukin-1beta, interleukin-11 was significantly elevated in periodontal disease [255]. Interleukin-11 is involved in bony resorption in cancer [256] and this has implications in regards its likely role in bony destruction in periodontal disease. The role of the endocrine system via parathyroid hormone (PTH) is significant too as PTH stimulated osteoclast formation through interleukin-11 and interleukin-6 receptor [252].…”

Section: Bone Homeostasis/physiology Cytokines Periodontal Disease mentioning

confidence: 99%

Preventing and Correcting Communicable and Non-Communicable Chronic Disease via Amlexanox – Dual ‘No-Nonsense’ and Inflammatory Axis Targeting

Loudon¹

2013

J Bioanal Biomed

View full text Add to dashboard Cite

In this sequel article on Amlexanox I investigate the multi-tasking potential for this drug, a recently discovered readthrough agent with immune-modulatory properties, for management of a wide range of human diseases including ageing modeled as a disease. The focus is not only on correction or disease rescue, but also on early prevention through use of Amlexanox prophylaxis. The concept of readthrough of nonsense mutations is further explored and correlation of nonsense mutation with cancer spread and stage is examined. Many other prevalent disease processes are examined in the light of nonsense-mediated causation, for example, intellectual disability and ageing. A primary aim of my current investigation is to show that both communicable diseases (related to infections from viral and bacterial agents) as well as non-communicable diseases (such as cancer, diabetes and inherited malformations/dysfunctions) may all form suited targets for Amlexanox therapy. As such, ex vivo and in vitro studies and animal models are discussed with the overall theme being to translate positive findings into the clinic. Clearly, this would have a major benefit with management in many inherited disease states and for infectious diseases. Further, a major benefit can be predicted for acquired chronic conditions too. The long understood property of Amlexanox in immune-modulation is exploited in this analysis. By acting through part-control of the NF-kappaB transcriptional factor-inflammatory axis, Amlexanox is capable of modulating the pathophysiology of such processes as cancer, vascular disease and diabetes with obesity. Moderating the response to pathogen challenge is a focus of attention in this present investigation. This is important insofar as Amlexanox mediates inflammatory-axis regulation and host-pathogen interactions, strongly suggesting that it must be explored in this context. As a result of this, interference with this arm of the innate immune system may well have consequences in terms of exposure to certain infectious agents. Detailed animal model systems as well as formal clinical trials are definitely called for to clarify the longer-term adverse reaction this may produce in the face of pathogen exposure. Amlexanox has been clinically approved for many years and, along with other drugs with similar immune-modulating capacity, appears satisfactory for long-term usage. Therefore, in practical terms, pathogen challenge in such a context may not pose significant threat. Overall, clinical trials are universally called for in order to ascertain the full potential for this old drug presenting with some exciting 'new tricks'. I aim to be able to purposefully 'repurpose' Amlexanox and add this drug into the 'Doctor's bag' as a highly valuable medical adjunct to manage a wide plethora of medical conditions.

show abstract

The early transcriptomic response to interleukin 1β and interleukin 33 in rat neonatal cardiomyocytes

Cited by 2 publications

References 23 publications

Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases

Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases

Preventing and Correcting Communicable and Non-Communicable Chronic Disease via Amlexanox – Dual ‘No-Nonsense’ and Inflammatory Axis Targeting

Contact Info

Product

Resources

About