TY - JOUR
T1 - Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages.
AU - O'Brien-Ladner, A. R.
AU - Nelson, M. E.
AU - Cowley, B. D.
AU - Bailey, K.
AU - Wesselius, L. J.
PY - 1995/3
Y1 - 1995/3
N2 - Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism.
AB - Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism.
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U2 - 10.1165/ajrcmb.12.3.7873193
DO - 10.1165/ajrcmb.12.3.7873193
M3 - Article
C2 - 7873193
AN - SCOPUS:0029267388
SN - 1044-1549
VL - 12
SP - 275
EP - 279
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 3
ER -