Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma.

Abstract

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-1alpha, but not the CXC chemokine MIP-2. The production of TNF- alpha 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.

• Authors: László Virág, Péter Bai, István Bak, Pál Pacher, Jon G Mabley, Lucas Liaudet, Edina Bakondi, Pál Gergely, Márk Kollai, Csaba Szabó
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 10 Issue 3 Pg. BR77-83 (Mar 2004) ISSN: 1234-1010 [Print] United States
• PMID: 14976461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CXCL2
• Chemokines
• Cxcl2 protein, mouse
• Cytokines
• Enzyme Inhibitors
• Interleukin-13
• Interleukin-5
• Poly(ADP-ribose) Polymerase Inhibitors
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• Ovalbumin
• Peroxidase

Topics

• Animals
• Asthma (drug therapy)
• Bronchoalveolar Lavage
• Catalysis
• Cell Death
• Cell Movement
• Chemokine CXCL2
• Chemokines (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Down-Regulation
• Enzyme Inhibitors (pharmacology)
• Interleukin-10 (metabolism)
• Interleukin-12 (metabolism)
• Interleukin-13 (metabolism)
• Interleukin-5 (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Lung (pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Ovalbumin (metabolism, pharmacology)
• Peroxidase (metabolism)
• Poly(ADP-ribose) Polymerase Inhibitors
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)