Adenosine A2A-Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 Production in Monocytes

Takahashi, Hideo; Kanke, Toru; Liu, Keyue; Yoshino, Tadashi; Sendo, Toshiaki; Tanaka, Noriaki; Nishibori, Masahiro

doi:10.1254/jphs.sc0070101

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…Our results showed the ability of adenosine to abolish the LPS-induced TNFα production in intestinal cell cultures (Fig. 2), in agreement with previous data [23]. However, adenosine had limited capacity to reduce (P<0.05) the PA2-or PA9-induced TNFα production.…”

Section: Discussionsupporting

confidence: 92%

Gliadins induce TNFα production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

Llopis

Sanz

2010

J Physiol Biochem

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Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to gliadins. In this study the effects of two gliadin-derived peptides (PA2, PQPQLPYPQPQLP and PA9, QLQPFPQPQLPY) on TNFalpha production by intestinal epithelial cells (Caco-2) and whether these effects were related to protein kinase A (PKA) and/or -C (PKC) activities have been evaluated. Caco-2 cell cultures were challenged with several sets of gliadin peptides solutions (0.25 mg/mL), with/without different activators of PKA or PKC, bradykinin (Brdkn) and pyrrolidine dithiocarbamate (PDTC). The gliadin-derived peptides assayed represent the two major immunodominant epitopes of the peptide 33-mer of alpha-gliadin (56-88) (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF). Both peptides induced the TNFalpha production triggering the inflammatory cell responses, the PA2 being more effective. The addition of the peptides in the presence of dibutyril cyclic AMP (cAMP), Brdkn or PDTC, inhibited the TNFalpha production. The PKC-activator phorbol 12-myristate 13-diacetate additionally increased the PA2- and PA9-induced TNFalpha production. These results link the gliadin-derived peptides induced TNFalpha production through cAMP-dependent PKA activation, where ion channels controlling calcium influx into cells could play a protective role, and requires NF-kappaB activation.

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Section: Discussionsupporting

confidence: 92%

Gliadins induce TNFα production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

Llopis

Sanz

2010

J Physiol Biochem

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“…A 1 R dysregulation leads to a proinflammatory state (11) and because of the high affinity of A 1 R (coupled to G i -protein) for adenosine, A 1 R blockade could potentially increase cAMP not only directly but also indirectly by displacing adenosine toward A 2a R (coupled to G s -protein), which ultimately will down-regulate TNF-␣ release (26,27). A 1 R is directly induced in response to infection and oxidative stress in multiple cells (28).…”

Section: Discussionmentioning

confidence: 99%

Caffeine Modulates TNF-α Production by Cord Blood Monocytes: The Role of Adenosine Receptors

et al. 2009

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Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A 1 R), ZM241385(A 2a R), MRS1754(A 2b R), and MRS1220(A 3 R). After 48 h in culture, A 2a R and A 2b R gene expression increased 1.9 (p ϭ 0.04) and 2.5-fold (p ϭ 0.003), respectively. A 1 R protein expression directly correlated with increasing LPS concentrations (p ϭ 0.01), with minimal expression preexposure. Only caffeine (50 M) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-␣) release from LPS activated-CBM by 20 and 25% (p ϭ 0.01) and TNF-␣ gene expression by 30 and 50%, respectively, in conjunction with a Ն2-fold increase in cAMP (p Ͻ 0.05). AR blockade did not modulate other measured cytokines. The induction of A 1 R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A 1 R blockade, increases cAMP production and inhibits pretranscriptional TNF-␣ production by CBM. (Pediatr Res 65: 203-208, 2009) C affeine (1,3,11 trimethylxantine) is a stimulant widely used in neonatology to treat apnea of prematurity (1). At therapeutic range (5 to 15 g/mL), caffeine blocks A 1 and A 2a adenosine receptors (ARs) stimulating ventilation (2-4). Recently, caffeine has also been linked to a decrease in the incidence of bronchopulmonary dysplasia and cerebral palsy in extremely premature infants (5,6), although the mechanisms explaining these findings have not been elucidated.The natural ligand for ARs, adenosine, has a crucial role in multiple biologic processes including inflammation (7,8). The increase in tumor necrosis factor-alpha (TNF-␣) release by adult peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) exposure can be abolished by pretreatment with A 2a R agonists (9,10). Adenosine binding to A 1 R (11,12) and A 3 R (13,14) also modulates TNF-␣ release from adult monocytes, whereas A 2b R appears to have little effect (10).Little is known about AR expression on neonatal monocytes and the role of caffeine in modulating cytokine release. We hypothesized that caffeine blockade of ARs on neonatal monocytes would increase the release of cytokines in response to LPS. To test this hypothesis, we used cord blood monocytes (CBM) from full-term infants to 1) characterize the changes in AR mRNA profile and protein expression after 48 h in ...

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“…However, the effect of P1 receptor agonists on cytokine release from human mononuclear cells was shown to depend on the specific Toll-like receptor (TLR) subtype used for stimulation: the A 2A agonist CGS21680 inhibited TLR4-mediated TNF-α release, but potentiated TLR3- and TLR5-mediated IL-6 release [ 192 ]. Activation of A 2A receptors also inhibited LPS-induced IL-18 production, expression of adhesion molecules and production of TNF-α, in human monocytes [ 193 , 194 ]. Activation of A 1 receptors promoted multinucleated giant cell formation by human monocytes [ 195 ].…”

Section: Purinergic Signalling In the Main Subsets Of Immune Cellsmentioning

confidence: 99%

Purinergic signalling and immune cells

Burnstock

Boeynaems

2014

Purinergic Signalling

254

222

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This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5′-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells.

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Adenosine A2A-Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 Production in Monocytes

Cited by 7 publications

References 15 publications

Gliadins induce TNFα production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

Gliadins induce TNFα production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

Caffeine Modulates TNF-α Production by Cord Blood Monocytes: The Role of Adenosine Receptors

Purinergic signalling and immune cells

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