Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated

Takahashi, Hideo; Ishibashi, Hiromi; Hamano, Ryosuke; Wake, Hidenori; Kanke, Toru; Liu, K; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

doi:10.1038/sj.bjp.0707126

Cited by 31 publications

(26 citation statements)

References 24 publications

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“…A 3 R activation has been linked to pro-and antiinflammatory effects, from pro-to antiinflammatory (14,26,32). Recently, A 3 R has been described as positively coupled to adenylyl cyclase, thereby increasing cAMP production upon activation (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Moreover, adenosine receptor stimulation has been shown to have a differential effect on the release of proinflammatory cytokines (21,22). In particular, stimulation of A 2A adenosine receptors inhibits TNF␣ production in human PBMCs (22)(23)(24). In RA patients, adenosine has been reported to suppress the elevated levels of proinflammatory cytokines, including TNF␣ and interleukin-1␤ (25).…”

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confidence: 99%

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Varani¹,

Massara²,

Vincenzi³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate A 1 , A 2A , A 2B , and A 3 adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti-tumor necrosis factor ␣ (anti-TNF␣), as compared with those in age-matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNF␣ release and NF-B activation.Methods. Adenosine receptors were analyzed by saturation binding assays and Western blot analyses.

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“…Recently, Reutershan et al [6] have also shown that treatment of animals with A 2A R agonists decreased lung inflammation by decreasing neutrophil infiltration into the lung alveoli. This reduction in neutrophil infiltration into the lungs observed in the present study as well as in earlier studies can be attributed to decreased expression of endothelial P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on these inflammatory cells [7].…”

Section: Discussionmentioning

confidence: 55%

2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia

Kumar

Harjai

Chhibber

2010

International Journal of Antimicrobial Agents

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Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated

Cited by 31 publications

References 24 publications

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

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

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia

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Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated

Cited by 31 publications

References 24 publications

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

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

Normalization of A2A and A3 adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia

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Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate