Abstract
Background and purpose: Adenosine suppresses immune responses through adenosine 2A (A 2A) receptors, by raising intracellular cAMP. Interleukin (IL)-18 up-regulates the expression of intercellular adhesion molecule (ICAM)-1 on monocytes, leading to production of pro-inflammatory cytokines such as IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α by human peripheral blood mononuclear cells (PBMC). We have previously demonstrated that elevation of cAMP inhibits this IL-18-induced expression of adhesion molecules. In the present study, we examined the effect of adenosine on the IL-18-induced up-regulation of ICAM-1 on human monocytes and production of IL-12, IFN-γ and TNF-α by PBMC. Experimental approach: The expression of ICAM-1 was examined by flow cytometry. IL-12, IFN-γ and TNF-α were determined by ELISA ass1ay. Key results: Adenosine inhibited the IL-18-induced up-regulation of ICAM-1 on human monocytes and it abolished the IL-18-enhanced production of IL-12, IFN-γ and TNF-α. While an A 2A receptor antagonist reversed the action of adenosine, an A 1 or A 3 receptor antagonist enhanced them. An A 2A receptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A 2A receptor antagonist but also by A 1 or A 3 receptor agonists. Activation via A 2A receptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A 1 or A 3 receptors inhibited it, suggesting that intracellular signal transduction following ligation of A 2A receptors might be blocked by activation of A 1 or A 3 receptors. Conclusions and Implications: Adenosine differentially regulates IL-18-induced adhesion molecule expression and cytokine production through several subtypes of its receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 816-822 |
| Number of pages | 7 |
| Journal | British Journal of Pharmacology |
| Volume | 150 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 18 2007 |
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Keywords
- Adenosine
- Cytokine
- Human peripheral blood mononuclear cells
- Intercellular adhesion molecule-1
- Interleukin-18
ASJC Scopus subject areas
- Pharmacology
Cite this
Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated. / Takahashi, H. K.; Iwagaki, H.; Hamano, R.; Wake, Hidenori; Kanke, T.; Liu, K.; Yoshino, Tadashi; Tanaka, N.; Nishibori, Masahiro.
In: British Journal of Pharmacology, Vol. 150, No. 6, 18.03.2007, p. 816-822.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated
AU - Takahashi, H. K.
AU - Iwagaki, H.
AU - Hamano, R.
AU - Wake, Hidenori
AU - Kanke, T.
AU - Liu, K.
AU - Yoshino, Tadashi
AU - Tanaka, N.
AU - Nishibori, Masahiro
PY - 2007/3/18
Y1 - 2007/3/18
N2 - Background and purpose: Adenosine suppresses immune responses through adenosine 2A (A 2A) receptors, by raising intracellular cAMP. Interleukin (IL)-18 up-regulates the expression of intercellular adhesion molecule (ICAM)-1 on monocytes, leading to production of pro-inflammatory cytokines such as IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α by human peripheral blood mononuclear cells (PBMC). We have previously demonstrated that elevation of cAMP inhibits this IL-18-induced expression of adhesion molecules. In the present study, we examined the effect of adenosine on the IL-18-induced up-regulation of ICAM-1 on human monocytes and production of IL-12, IFN-γ and TNF-α by PBMC. Experimental approach: The expression of ICAM-1 was examined by flow cytometry. IL-12, IFN-γ and TNF-α were determined by ELISA ass1ay. Key results: Adenosine inhibited the IL-18-induced up-regulation of ICAM-1 on human monocytes and it abolished the IL-18-enhanced production of IL-12, IFN-γ and TNF-α. While an A 2A receptor antagonist reversed the action of adenosine, an A 1 or A 3 receptor antagonist enhanced them. An A 2A receptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A 2A receptor antagonist but also by A 1 or A 3 receptor agonists. Activation via A 2A receptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A 1 or A 3 receptors inhibited it, suggesting that intracellular signal transduction following ligation of A 2A receptors might be blocked by activation of A 1 or A 3 receptors. Conclusions and Implications: Adenosine differentially regulates IL-18-induced adhesion molecule expression and cytokine production through several subtypes of its receptors.
AB - Background and purpose: Adenosine suppresses immune responses through adenosine 2A (A 2A) receptors, by raising intracellular cAMP. Interleukin (IL)-18 up-regulates the expression of intercellular adhesion molecule (ICAM)-1 on monocytes, leading to production of pro-inflammatory cytokines such as IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α by human peripheral blood mononuclear cells (PBMC). We have previously demonstrated that elevation of cAMP inhibits this IL-18-induced expression of adhesion molecules. In the present study, we examined the effect of adenosine on the IL-18-induced up-regulation of ICAM-1 on human monocytes and production of IL-12, IFN-γ and TNF-α by PBMC. Experimental approach: The expression of ICAM-1 was examined by flow cytometry. IL-12, IFN-γ and TNF-α were determined by ELISA ass1ay. Key results: Adenosine inhibited the IL-18-induced up-regulation of ICAM-1 on human monocytes and it abolished the IL-18-enhanced production of IL-12, IFN-γ and TNF-α. While an A 2A receptor antagonist reversed the action of adenosine, an A 1 or A 3 receptor antagonist enhanced them. An A 2A receptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A 2A receptor antagonist but also by A 1 or A 3 receptor agonists. Activation via A 2A receptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A 1 or A 3 receptors inhibited it, suggesting that intracellular signal transduction following ligation of A 2A receptors might be blocked by activation of A 1 or A 3 receptors. Conclusions and Implications: Adenosine differentially regulates IL-18-induced adhesion molecule expression and cytokine production through several subtypes of its receptors.
KW - Adenosine
KW - Cytokine
KW - Human peripheral blood mononuclear cells
KW - Intercellular adhesion molecule-1
KW - Interleukin-18
UR - http://www.scopus.com/inward/record.url?scp=33947324677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947324677&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0707126
DO - 10.1038/sj.bjp.0707126
M3 - Article
C2 - 17310143
AN - SCOPUS:33947324677
VL - 150
SP - 816
EP - 822
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 6
ER -