Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in murine models of inflammatory lung injury Article

Moreno-Vinasco, L, Quijada, H, Sammani, S et al. (2014). Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in murine models of inflammatory lung injury . AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 51(2), 223-228. 10.1165/rcmb.2012-0519OC

cited authors

  • Moreno-Vinasco, L; Quijada, H; Sammani, S; Siegler, J; Letsiou, E; Deaton, R; Saadat, L; Zaidi, RS; Messana, J; Gann, PH; Machado, RF; Ma, W; Camp, SM; Wang, T; Garcia, JGN

authors

abstract

  • We previously identified the intracellular nicotinamide phosphoribosyltransferase (iNAMPT, aka pre-B-cell colony enhancing factor) as a candidate gene promoting acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing NF-κB signaling in lung endothelium. iNAMPT also synthesizes intracellular nicotinamide adenine dinucleotide (iNAD) in response to extracellular oxidative stress, contributing to the inhibition of apoptosis via ill-defined mechanisms. We now further define the role of iNAMPT activity in the pathogenesis of ARDS/VILI using the selective iNAMPT inhibitor FK-866. C57/B6 mice were exposed to VILI (40 ml/kg, 4 h) or LPS (1.5 mg/kg, 18 h) after osmotic pump delivery of FK-866 (100 mg/kg/d, intraperitoneally). Assessment of total bronchoalveolar lavage (BAL) protein, polymorphonuclear neutrophil (PMN) levels, cytokine levels (TNFα, IL-6, IL-1α), lung iNAD levels, and injury scores revealed that FK-866-mediated iNAMPT inhibition successfully reduced lung tissue iNAD levels, BAL injury indices, inflammatory cell infiltration, and lung injury scores in LPS- and VILI-exposed mice. FK-866 further increased lungPMNapoptosis, as reflected by caspase-3 activation in BAL PMNs. These findings support iNAMPT inhibition via FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in inflammatory PMNs. Copyright © 2014 by the American Thoracic Society.

publication date

  • January 1, 2014

published in

Digital Object Identifier (DOI)

start page

  • 223

end page

  • 228

volume

  • 51

issue

  • 2