Lipopolysaccharide; Lung inflammation; Pulmonary drug delivery; Neutrophil recruitment
Abstract :
[en] Neutrophils constitute the first line of host defense against invading microorganisms. Yet their removal from the inflammatory environment is fundamental for injury restraint and resolution of inflammation. Nicotinamide, a component of vitamin B(3), is known to modulate cell survival. In this study, we assessed the influence of nicotinamide on neutrophil apoptosis, both in vitro and in vivo in a mouse model of endotoxin-induced lung inflammation. In vitro, nicotinamide promoted apoptosis of human blood neutrophils in a dose-dependent manner in the presence of the apoptosis inhibitors granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor. The highest concentration of nicotinamide completely neutralized the pro-survival effect of granulocyte (macrophage) colony-stimulating factor. Nicotinamide proapoptotic effect was associated with enhanced caspase-3 activity. In addition, nicotinamide slightly reduced neutrophil chemotaxis in vitro. In vivo, pulmonary nicotinamide delivery decreased the levels of cellular and biochemical inflammation markers and increased the percentage of apoptotic neutrophils in bronchoalveolar lavages. Our findings suggest that nicotinamide is an apoptotic stimulus for neutrophils, thereby contributing to the resolution of neutrophilic inflammation in the lungs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Fernandes, Claudia A. ✱; Unité de Pharmacie Galénique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels
Fievez, Laurence ✱; Université de Liège - ULiège > Département de sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Ucakar, Bernard; Unité de Pharmacie Galénique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels
Neyrinck, Audrey M.; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain
Fillee, Catherine; Université Catholique de Louvain - UCL > Department of Clinical Biology, Cliniques Universitaires Saint Luc,
Huaux, Francois; Université Catholique de Louvain - UCL > Louvain Centre for Toxicology and Applied Pharmacology
Delzenne, Nathalie M.; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain
Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Vanbever, Rita; Unité de Pharmacie Galénique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels
✱ These authors have contributed equally to this work.
Language :
English
Title :
Nicotinamide enhances apoptosis of G(M)-CSF-treated neutrophils and attenuates endotoxin-induced airway inflammation in mice.
Publication date :
2011
Journal title :
American Journal of Physiology - Lung Cellular and Molecular Physiology
ISSN :
1040-0605
eISSN :
1522-1504
Publisher :
American Physiological Society, United States - Maryland
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