Induction of murine adenosine A2A receptor expression by LPS: analysis of the 5′ upstream promoter

Elson, Genie; Eisenberg, Marcia; Garg, Chanchal; Outram, Shalini Persaud; Ferrante, Christopher; Haskó, György; Leibovich, Samuel

doi:10.1038/gene.2012.60

Cited by 22 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This change was not surprising as, in prior studies, we and others had demonstrated that there is upregulation of both A2AR receptor expression and function following exposure to inflammatory stimuli (IL-1β and tumour necrosis factor (TNF)) which acts as a feedback regulator of inflammation in both murine and human cells323334353637. One explanation for the difference between A2AR expression in human and murine OA cartilage is that the findings in A2AR KO mice do not reflect OA development in humans.…”

Section: Resultsmentioning

confidence: 72%

Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression

et al. 2017

View full text Add to dashboard Cite

Osteoarthritis (OA) is characterized by cartilage destruction and chondrocytes have a central role in this process. With age and inflammation chondrocytes have reduced capacity to synthesize and maintain ATP, a molecule important for cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its metabolite, fall after treatment of mouse chondrocytes and rat tibia explants with IL-1β, an inflammatory mediator thought to participate in OA pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5′nucleotidase (an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA and chondrocytes lacking A2AR develop an ‘OA phenotype' with increased expression of Mmp13 and Col10a1. Adenosine replacement by intra-articular injection of liposomal suspensions containing adenosine prevents development of OA in rats. These results support the hypothesis that maintaining extracellular adenosine levels is an important homeostatic mechanism, loss of which contributes to the development of OA; targeting adenosine A2A receptors might treat or prevent OA.

show abstract

Section: Resultsmentioning

confidence: 72%

Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Increased activity of CD73 (5=-ectonucleotidase), the main regulator of adenosine metabolism, has been documented in exercising rats (38). We and others have shown that adenosine receptor expression can rapidly be increased in the presence of adenosine itself or stress induced by the addition of lipopolysaccharide (16,17,53,76,80). This is the first report showing that adenosine receptors are upregulated by continuous exercise.…”

Section: Adenosine Receptors Are Upregulated By Exercise: a Potentialmentioning

confidence: 70%

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Puhl

Müller

Wagner

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Although exercise mediates beneficial effects in patients after myocardial infarction (MI), the underlying mechanisms as well as the question of whether an early start of exercise after MI is safe or even beneficial are incompletely resolved. The present study analyzed the effects of exercise before and reinitiated early after MI on cardiac remodeling and function. Male C57BL/6N mice were housed sedentary or with the opportunity to voluntarily exercise for 6 wk before MI induction (ligation of the left anterior descending coronary artery) or sham operation. After a 5-day exercise-free phase after MI, mice were allowed to reexercise for another 4 wk. Exercise before MI induced adaptive hypertrophy with moderate increases in heart weight, cardiomyocyte diameter, and left ventricular (LV) end-diastolic volume, but without fibrosis. In sedentary mice, MI induced eccentric LV hypertrophy with massive fibrosis but maintained systolic LV function. While in exercised mice gross LV end-diastolic volumes and systolic function did not differ from sedentary mice after MI, LV collagen content and thinning of the infarcted area were reduced. This was associated with ameliorated activation of inflammation, mediated by TNF-␣, IL-1␤, and IL-6, as well as reduced activation of matrix metalloproteinase 9. In contrast, no differences in the activation patterns of various MAPKs or adenosine receptor expressions were observed 5 wk after MI in sedentary or exercised mice. In conclusion, continuous exercise training before and with an early reonset after MI ameliorates adverse LV remodeling by attenuating inflammation, fibrosis, and scar thinning. Therefore, an early reonset of exercise after MI can be encouraged. exercise; remodeling; scar thinning; magnetic resonance imaging; fibrosis; myocardial infarction NEW & NOTEWORTHY Our data provide new insights into the exercise-mediated cardioprotection by implying that an early reinitiation of exercise after myocardial infarction attenuates left ventricular fibrosis and scar thinning, presumably by attenuating the coordinated proinflammatory response involving TNF-␣, IL-6, and IL-1␤. These findings could translate into clinical benefits in patients.CORONARY ARTERY DISEASE is the single most frequent cause of death worldwide. In Europe, every sixth man and every seventh woman will die of myocardial infarction (MI) (71). Those patients who survive MI frequently develop systolic heart failure due to the infarct-induced loss of functional myocardium per se and remodeling of the remainder of the left ventricular (LV) myocardium, which is frequently associated with thinning of the LV wall in the area of MI and its border zone, LV dilation, and systolic dysfunction. These parameters of myocardial remodeling are important prognostic markers for the long-term outcome of these patients. For instance, regional wall thinning is associated with postinfarction ventricular arrhythmia (36) and adverse outcome in patients undergoing coronary artery bypass surgery (87).Scar formation occurs secondary to isc...

show abstract

“…Previous studies have shown the up-regulation of A 2A Rs in macrophages activated by LPS stimulation [16–19]. This up-regulation is believed to sensitize macrophages to adenosine signaling by priming M1 macrophages to respond to adenosine and thus switching toward the M2d phenotype.…”

Section: Resultsmentioning

confidence: 96%

The Adenosine-Dependent Angiogenic Switch of Macrophages to an M2-Like Phenotype is Independent of Interleukin-4 Receptor Alpha (IL-4Rα) Signaling

et al. 2013

View full text Add to dashboard Cite

Murine macrophages are activated by interferon-γ (IFNγ) and/or TLR agonists such as bacterial endotoxin (LPS) to express an inflammatory (M1) phenotype characterized by expression of nitric oxide synthase-2 (iNOS) and inflammatory cytokines such as TNF-α and IL-12. In contrast, Th2 cytokines IL-4 and IL-13 activate macrophages by inducing expression of arginase-1 and the anti-inflammatory cytokine IL-10 in an IL-4 receptor-α (IL-4Rα) dependent manner. Macrophages activated in this way are designated as “alternatively activated” (M2a) macrophages. We have shown previously that adenosine A2A receptor (A2AR) agonists act synergistically with TLR2, 4, 7 and 9 agonists to switch macrophages into an “M2-like” phenotype that we have termed “M2d”. Adenosine signaling suppresses TLR-dependent expression of TNF-α, IL-12, IFN-γ and several other inflammatory cytokines by macrophages, and induces expression of VEGF and IL-10. We show here using mice lacking a functional IL-4Rα gene (IL-4Rα−/− mice) that this adenosine-mediated switch does not require IL-4Rα-dependent signaling. M2d macrophages express high levels of VEGF, IL-10 and iNOS, low levels of TNF-α and IL-12, and mildly elevated levels of arginase-1. In contrast, M2d macrophages do not express Ym1, Fizz1 (RELM-α) or CD206 at levels greater than those induced by LPS, and dectin-1 expression is suppressed. Use of these markers in vivo to identify “M2” macrophages thus provides an incomplete picture of macrophage functional status and should be viewed with caution.

show abstract

Induction of murine adenosine A2A receptor expression by LPS: analysis of the 5′ upstream promoter

Cited by 22 publications

References 35 publications

Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression

Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

The Adenosine-Dependent Angiogenic Switch of Macrophages to an M2-Like Phenotype is Independent of Interleukin-4 Receptor Alpha (IL-4Rα) Signaling

Contact Info

Product

Resources

About