The anti-inflammatory target A3 adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn’s disease

Ochaion, Avivit; Bar-Yehuda, Sara; Cohen, Shira; Barer, Faina; Patoka, R.; Amital, Howard; Reitblat, Tatiana; Reitblat, A.; Ophir, J; Konfino, I.; Chowers, Yehuda; Ben‐Horin, Shomron; Fishman, Pnina

doi:10.1016/j.cellimm.2009.03.020

Cited by 109 publications

(94 citation statements)

References 30 publications

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“…Some observations suggest that purine metabolism could be defective in skin autoimmune diseases such as psoriasis (Kiehl and Ionescu, 1992;Kose et al, 2001); overexpression of A 2A and A 3 AR in inflammatory cells has been found in different autoimmune disorders (Ochaion et al, 2009;Varani et al, 2011). In this study, we have observed a reduction in A 2B AR expression besides the increased expression of A 2A AR in psoriatic epidermis.…”

Section: Discussionsupporting

confidence: 43%

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Andrés

Terencio

Arasa

et al. 2017

Journal of Investigative Dermatology

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Adenosine is a potent regulator of inflammation and immunity, but the role of adenosine receptors in keratinocytes remains controversial. We determined that in addition to A 2B receptors, human epidermal keratinocytes also express A 2A receptors, although to a lower extent. Through the use of selective adenosine receptor agonists and antagonists, we showed that physiological concentrations of adenosine activate A 2B receptors in normal human keratinocytes, inducing cell cycle arrest through the increase of intracellular calcium but not through cAMP signaling. In contrast, the selective activation of A 2A receptors by CGS-21680 induces keratinocyte proliferation via p38emitogen-activated protein kinase activation. Adenosine and selective A 2A and A 2B agonists presented anti-inflammatory profiles independent of adenosine receptors but mediated by membrane phosphatase activation. Finally, keratinocyte exposure to diverse inflammatory cytokines altered adenosine receptor expression by reducing A 2B and increasing A 2A , a pattern also observed in psoriatic epidermis. Because increased epidermal turnover and inflammatory response are characteristics of psoriatic disease, further studies are needed to assess the role and consequences of the altered adenosine receptor expression in lesional and nonlesional psoriatic keratinocytes.

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Section: Discussionsupporting

confidence: 43%

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Andrés

Terencio

Arasa

et al. 2017

Journal of Investigative Dermatology

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“…S4). Previous studies have demonstrated that the activity of p38, ERK1/2 and PI3K/Akt were increased in lesional psoriatic skin (31,32). Our results showed that HK had excellent inhibition effect on phosphorylated ERK1/2 and AKT.…”

Section: Discussionsupporting

confidence: 56%

Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

Wen

Pei

et al. 2015

Journal of Pharmacological Sciences

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Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has been reported to possess anti-inflammatory and anti-angiogenic activaties. In this study, our aim was to investigate anti-psoriatic activities of HK and the involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and TNF-α-induced NF-κB (p65) activation were analyzed by respective FCS and immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2 cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65 activation, as well as other angiogenic and inflammatory parameters were studied by immunostainings. Importantly, we found that HK significantly decreased the ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-α-induced activation of NF-κB. The morphology and histological features of psoriasis were effectively improved by HK treatment. The expression of TNF-α and IFN-γ, and their corresponding mRNA levels were down-regulated and the expression of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p-ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our study suggested that HK exhibits anti-psoriatic effects through the inhibition of NF-κB and VEGFR-2.

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“…Furthermore, A 3 AR density inversely correlates with Disease Activity Score in 28 or 44 joints, suggesting a direct role of the endogenous activation of these receptors in the control of RA inflammation (Varani et al, 2011b). The overexpression of A 3 ARs in RA has been directly linked to the increase in NF-kB, a key player in the pathogenesis of arthritic diseases Ochaion et al, 2009).…”

Section: E Rheumatoid Arthritis and Ostheoarthritismentioning

confidence: 99%

The A₃Adenosine Receptor: History and Perspectives

et al. 2014

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The anti-inflammatory target A3 adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn’s disease

Cited by 109 publications

References 30 publications

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

The A₃Adenosine Receptor: History and Perspectives

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The anti-inflammatory target A3 adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn’s disease

Cited by 109 publications

References 30 publications

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

The A3Adenosine Receptor: History and Perspectives

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Product

Resources

About

The A₃Adenosine Receptor: History and Perspectives