Nicotine enhances expression of the neutrophil elastase gene and protein in a human myeloblast/promyelocyte cell line.
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 microM 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.
Department of Medicine, New York University Medical Center, New York, New York, USA.
L W
LW
Armstrong
W N
WN
Rom
F T
FT
Martiniuk
D
D
Hart
J
J
Jagirdar
M
M
Galdston
D002478:Cells, Cultured / Q000187:drug effects; D005434:Flow Cytometry; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D019272:Leukocyte Elastase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000302:isolation & purification; D015854:Up-Regulation
D005731:Ganglionic Stimulants; D012333:RNA, Messenger; D009538:Nicotine; D019272:Leukocyte Elastase