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Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors

Overview of attention for article published in Arthritis Research & Therapy, September 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (66th percentile)

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Title
Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors
Published in
Arthritis Research & Therapy, September 2015
DOI 10.1186/s13075-015-0771-6
Pubmed ID
Authors

Miguel Perez-Aso, M. Carmen Montesinos, Aránzazu Mediero, Tuere Wilder, Peter H. Schafer, Bruce Cronstein

Abstract

This work was undertaken to delineate intracellular signaling pathways for the PDE4 inhibitor apremilast and to examine interactions between apremilast, methotrexate and adenosine A2A receptors (A2AR). After apremilast and LPS incubation, intracellular cAMP, TNF-α, IL-10, IL-6 and IL-1α were measured in the Raw264.7 monocytic murine cell line. PKA, Epac1/2 (signaling intermediates for cAMP) and A2AR knockdowns were performed by shRNA transfection and interactions with A2AR and A2BR, as well as with methotrexate were tested in vitro and in the murine air pouch model. Statistical differences were determined using one or two-way ANOVA or Student's t test. The alpha nominal level was set at 0.05 in all cases. A P value of < 0.05 was considered significant. In vitro, apremilast increased intracellular cAMP and inhibited TNF-α release (IC50=104nM) and the specific A2AR-agonist CGS21680 (1μM) increased apremilast potency (IC50=25nM). In this cell line, apremilast increased IL-10 production. PKA, Epac1 and Epac2 knockdowns prevented TNF-α inhibition and IL-10 stimulation by apremilast. In the murine air pouch model, both apremilast and MTX significantly inhibited leukocyte infiltration, while apremilast, but not MTX, significantly inhibited TNF-α release. The addition of MTX (1 mg/kg) to apremilast (5 mg/kg) yielded no more inhibition of leukocyte infiltration or TNF-α release than with apremilast alone. The immunoregulatory effects of apremilast appear to be mediated by cAMP through the downstream effectors PKA, Epac1, and Epac2. A2AR agonism potentiated TNF-α inhibition by apremilast, consistent with the cAMP-elevating effects of that receptor. Because the A2AR is also involved in the anti-inflammatory effects of MTX, the mechanism of action of both drugs involves cAMP-dependent pathways and is therefore partially overlapping in nature.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 66 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 14%
Researcher 8 12%
Student > Master 8 12%
Student > Bachelor 6 9%
Other 6 9%
Other 15 23%
Unknown 14 21%
Readers by discipline Count As %
Medicine and Dentistry 11 17%
Agricultural and Biological Sciences 8 12%
Pharmacology, Toxicology and Pharmaceutical Science 8 12%
Immunology and Microbiology 7 11%
Biochemistry, Genetics and Molecular Biology 7 11%
Other 10 15%
Unknown 15 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2022.
All research outputs
#6,938,557
of 22,029,478 outputs
Outputs from Arthritis Research & Therapy
#1,403
of 2,917 outputs
Outputs of similar age
#82,942
of 257,608 outputs
Outputs of similar age from Arthritis Research & Therapy
#1
of 1 outputs
Altmetric has tracked 22,029,478 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 2,917 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 257,608 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them