TY - JOUR
T1 - Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma
AU - Virág, László
AU - Bai, Péter
AU - Bak, István
AU - Pacher, Pál
AU - Mabley, Jon
AU - Liaudet, Lucas
AU - Bakondi, Edina
AU - Gergely, Pál
AU - Kollai, Márk
AU - Szabó, Csaba
PY - 2004/3
Y1 - 2004/3
N2 - Background: Poly(ADP-ribose) polymerase-1 (PARP-1), a monomeric nuclear enzyme present in eukaryotes, plays a role in cell death, inflammatory mediator expression, and mononuclear cell recruitment in various experimental models of inflammation and reperfusion injury. Part of the molecular mechanism of this function involves the regulation of cytokine and chemokine production. Since chemokines are principal regulators of mononuclear and polymorphonuclear cell trafficking in asthma, we investigated the possibility whether PARP modulates chemokine production and cell recruitment in a murine model of asthma. Material/Methods: We studied ovalbumin-sensitized mice challenged with a single dose of ovalbumin. Results: PARP inhibition with the phenanthridinone-based PARP inhibitor PJ34 suppressed inflammatory cell migration. These effects were associated with downregulation of the CC chemokine MIP-1α, but not the CXC chemokine MIP-2. The production of TNF-α and IL-12, but not IL-5 or IL-13, was also suppressed by PARP inhibition. Conclusions: Our results demonstrate the pathogenetic role of PARP activation in a murine model of asthma. PARP selectively regulates the production of certain chemokines and cytokines in this experimental model, which may be responsible for some of the observed protective effects seen in the current murine asthma model.
AB - Background: Poly(ADP-ribose) polymerase-1 (PARP-1), a monomeric nuclear enzyme present in eukaryotes, plays a role in cell death, inflammatory mediator expression, and mononuclear cell recruitment in various experimental models of inflammation and reperfusion injury. Part of the molecular mechanism of this function involves the regulation of cytokine and chemokine production. Since chemokines are principal regulators of mononuclear and polymorphonuclear cell trafficking in asthma, we investigated the possibility whether PARP modulates chemokine production and cell recruitment in a murine model of asthma. Material/Methods: We studied ovalbumin-sensitized mice challenged with a single dose of ovalbumin. Results: PARP inhibition with the phenanthridinone-based PARP inhibitor PJ34 suppressed inflammatory cell migration. These effects were associated with downregulation of the CC chemokine MIP-1α, but not the CXC chemokine MIP-2. The production of TNF-α and IL-12, but not IL-5 or IL-13, was also suppressed by PARP inhibition. Conclusions: Our results demonstrate the pathogenetic role of PARP activation in a murine model of asthma. PARP selectively regulates the production of certain chemokines and cytokines in this experimental model, which may be responsible for some of the observed protective effects seen in the current murine asthma model.
KW - Chemokine
KW - Cytokine
KW - Macrophage inflammatory protein
KW - Poly(ADP-ribose) polymerase
KW - Tumor necrosis factor
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M3 - Article
C2 - 14976461
AN - SCOPUS:12144291327
SN - 1234-1010
VL - 10
SP - BR77-BR83
JO - Medical Science Monitor
JF - Medical Science Monitor
IS - 3
ER -