Mono ADP-ribosylation inhibitors prevent inflammatory cytokine release in alveolar epithelial cells

A549, a type II alveolar epithelial cell line stimulated with LPS (10 μg/ml), released high levels of the inflammatory cytokines IL-6 and IL-8. Here, we have investigated whether ADP-ribosylation inhibitors block the LPS-triggered cytokine release in epithelial cells. When coincubating A549 with LPS...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2008-03, Vol.310 (1-2), p.77-83
Main Authors: Del Vecchio, Mariangela, Balducci, Enrico
Format: Article
Language:English
Subjects:
3-Iodobenzylguanidine - pharmacology
Adenosine diphosphate
ADP Ribose Transferases - antagonists & inhibitors
ADP Ribose Transferases - metabolism
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell Line
Cells
Epithelial Cells - drug effects
Epithelial Cells - enzymology
Epithelial Cells - secretion
GPI-Linked Proteins
Humans
Inflammation Mediators - metabolism
Inhibitors
Interleukin-6 - secretion
Interleukin-8 - secretion
Life Sciences
Medical Biochemistry
Novobiocin - pharmacology
Oncology
Proteins
Pulmonary Alveoli - cytology
Pulmonary Alveoli - drug effects
Pulmonary Alveoli - enzymology
Pulmonary Alveoli - secretion
Studies
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Summary:A549, a type II alveolar epithelial cell line stimulated with LPS (10 μg/ml), released high levels of the inflammatory cytokines IL-6 and IL-8. Here, we have investigated whether ADP-ribosylation inhibitors block the LPS-triggered cytokine release in epithelial cells. When coincubating A549 with LPS and meta-iodobenzylguanidine or novobiocin, selective arginine-dependent ART-inhibitors, the release of IL-6 and IL-8 was inhibited in a concentration-dependent manner. This effect has been linked with the presence of a functionally active arginine ADP-ribosylating enzyme on the cell surface. To this aim, we amplified by RT-PCR the ART1 transcript and identified four ADP-ribosylated proteins likely substrate for ART1. The mechanism behind the cytokine inhibition in epithelial cells seems to be correlated with the presence of ART1, which behaves as an essential positive regulator of inflammatory cytokines. This novel observation indicates this enzyme as well as other novobiocin/MIBG sensitive ARTs as potential targets for the development of new therapeutic strategies.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-007-9667-3