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Titolo:
Adenosine inhibits macrophage colony-stimulating factor-dependent proliferation of macrophages through the induction of p27(kip-1) expression
Autore:
Xaus, J; Valledor, AF; Cardo, M; Marques, L; Beleta, J; Palacios, JM; Celada, A;
Indirizzi:
Univ Barcelona, Fac Biol, Dept Fisiol Biol Macrofag, E-08028 Barcelona, Spain Univ Barcelona Barcelona Spain E-08028 acrofag, E-08028 Barcelona, Spain Univ Barcelona, Fundacio August Pi & Sunyer, E-08028 Barcelona, Spain UnivBarcelona Barcelona Spain E-08028 Sunyer, E-08028 Barcelona, Spain Labs Almirali Prodesfarma SA, Res Ctr, Barcelona, Spain Labs Almirali Prodesfarma SA Barcelona Spain Res Ctr, Barcelona, Spain
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 8, volume: 163, anno: 1999,
pagine: 4140 - 4149
SICI:
0022-1767(19991015)163:8<4140:AIMCFP>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE-PHOSPHATASE; CELL-CYCLE; FACTOR-I; G1 PHASE; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; DNA-SYNTHESIS; TNF-ALPHA; RAT-BRAIN; KINASE-C;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
78
Recensione:
Indirizzi per estratti:
Indirizzo: Celada, A Univ Barcelona, Fac Biol, Dept Fisiol, Av Diagonal 645, E-08028 Barcelona,Spain Univ Barcelona Av Diagonal 645 Barcelona Spain E-08028 na,Spain
Citazione:
J. Xaus et al., "Adenosine inhibits macrophage colony-stimulating factor-dependent proliferation of macrophages through the induction of p27(kip-1) expression", J IMMUNOL, 163(8), 1999, pp. 4140-4149

Abstract

Adenosine is produced during inflammation and modulates different functional activities in macrophagcs, In murine bone marrow-derived macrophages, adenosine inhibits M-CSF-dependent proliferation with an IC50 of 45 mu M. Only specific agonists that can activate A(2B) adenosine receptors such as 5'-N-ethylcarboxamidoadenosine, but not those active on A(1) (N-6-(R)-phenylisopropyladenosine), A(2A) ([p-(2-carbonylethyl)phenplethylamino]-5'-N-ethylcarboxamidoadenosine), or A(3) (N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide) receptors, induce the generation of cAMP and modulate macrophage proliferation. This suggests that adenosine regulates macrophage proliferation by interacting with the A,, receptor and subsequently inducing the production of cAMP, In fact, both 8-Br-cAMP (IC50 85 mu M) and forskolin (IC50 7 muM) inhibit macrophage proliferation. Moreover, the inhibition of adenylyl cyclase and protein kinase A blocks the inhibitory effect of adenosine and its analogues on macrophage proliferation. Adenosine causes an arrest of macrophages at the G(1) phase of the cell cycle without altering the activation of the extracellular-regulated protein kinase pathway. The treatment of macrophages with adenosine induces the expression of p27(kip-1), a G(1) cyclin-dependent kinase inhibitor, in a protein kinase A-dependent way, Moreover, the involvement of p27(kip-1) in the adenosine inhibition of macrophageproliferation was confirmed using macrophages from mice with a disrupted p27(kip-1) gene. These results demonstrate that adenosine inhibits macrophage proliferation through a mechanism that involves binding to A,, adenosine receptor, the generation of cAMP, and the induction of p27(kip-1) expression.

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Documento generato il 10/07/20 alle ore 00:20:37