TY - JOUR
T1 - Nicotine enhances expression of the neutrophil elastase gene and protein in a human myeloblast/promyelocyte cell line
AU - Armstrong, Linda W.
AU - Rom, William N.
AU - Martiniuk, Frank T.
AU - Hart, David
AU - Jagirdar, Jaishree
AU - Galdston, Morton
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - The pathogenesis of emphysema is considered to be an imbalance of protease and antiprotease activity in the lower respiratory tract leading to uninhibited degradation of lung interstitium by elastolytic enzymes. An increased amount of the serine protease neutrophil elastase (NE) is though to play a major role in this degradation. Because the expression of NE is limited to neutrophil precursors in the bone marrow, we hypothesized that nicotine, which is readily absorbed from lung and distributed to tissue, including bone marrow, would increase expression of the NE gene and protein. HL-60 cells, a myeloblast/promyelocyte cell line, were cultured in the presence or absence of 0.06 and 0.8 μM nicotine for 5 d. Both concentrations of nicotine caused a 2.4- to 3.3-fold increase, respectively, in NE gene expression over unstimulated cells, and NE protein increased 4.8- to 3.4- fold over unstimulated cells, respectively, similar to our positive control DMSO. Nicotine did not induce upregulation of the NE gene by initiating cell differentiation. Both low and high nicotine concentrations upregulate the NE gene in HL-60 cells leading to increased NE protein concentration per cell suggesting a pathophysiologic mechanism for emphysema.
AB - The pathogenesis of emphysema is considered to be an imbalance of protease and antiprotease activity in the lower respiratory tract leading to uninhibited degradation of lung interstitium by elastolytic enzymes. An increased amount of the serine protease neutrophil elastase (NE) is though to play a major role in this degradation. Because the expression of NE is limited to neutrophil precursors in the bone marrow, we hypothesized that nicotine, which is readily absorbed from lung and distributed to tissue, including bone marrow, would increase expression of the NE gene and protein. HL-60 cells, a myeloblast/promyelocyte cell line, were cultured in the presence or absence of 0.06 and 0.8 μM nicotine for 5 d. Both concentrations of nicotine caused a 2.4- to 3.3-fold increase, respectively, in NE gene expression over unstimulated cells, and NE protein increased 4.8- to 3.4- fold over unstimulated cells, respectively, similar to our positive control DMSO. Nicotine did not induce upregulation of the NE gene by initiating cell differentiation. Both low and high nicotine concentrations upregulate the NE gene in HL-60 cells leading to increased NE protein concentration per cell suggesting a pathophysiologic mechanism for emphysema.
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U2 - 10.1164/ajrccm.154.5.8912774
DO - 10.1164/ajrccm.154.5.8912774
M3 - Article
C2 - 8912774
AN - SCOPUS:0029820141
VL - 154
SP - 1520
EP - 1524
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 5
ER -