Nicotinamide enhances apoptosis of G(M)-CSF-treated neutrophils and attenuates endotoxin-induced airway inflammation in mice.
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.
Unité de Pharmacie Galénique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Cláudia A
CA
Fernandes
Laurence
L
Fievez
Bernard
B
Ucakar
Audrey M
AM
Neyrinck
Catherine
C
Fillee
François
F
Huaux
Nathalie M
NM
Delzenne
Fabrice
F
Bureau
Rita
R
Vanbever
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D004731:Endotoxins; D004789:Enzyme Activation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D009536:Niacinamide / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D054426:Chemokine CXCL2; D018925:Chemokines; D004731:Endotoxins; C074302:keratinocyte-derived chemokines; D009536:Niacinamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3