Oxidative Stress - Chronic Obstructive Pulmonary Disease - page 308

Figure 13 Oxidative stress = cigarette smoke can cause increased gene expression of
both pro-inflammatory genes and also activation of protective genes, such as g -glu-
tamylcysteine synthetase. During sustained = chronic inflammation, the balance
between genes for inflammatory mediators and antioxidant = phase II enzymes may
be tipped in favor of pro-inflammatory mediators. It is possible that oxidative stress
is enhanced during repair process by decreasing the GSH levels leading to pathology.
Maestrelli et al. (98) have shown that heme oxygenase-1 (HO-1) is
induced in alveolar spaces of smokers suggesting that oxidative stress due
to cigarette smoke may increase the gene expression of HO-1 leading to
increased levels of exhaled CO (98). Cigarette smoke also induces heat shock
protein 70 (HS 70) in human monocytes and HO-1, which have been
implicated in the regulation of cell injury and cell death and, in particular,
modulation of apoptosis in human endothelial cells and monocytes (99).
Thus oxidative stress, including that produced by cigarette smoke,
causes increased gene expression of both pro-inflammatory genes and also
activation of protective antioxidant genes. A balance may therefore exist
between pro- and anti-inflammatory gene expression in response to cigarette
smoke, which may be critical to whether cell injury is induced by cigarette
smoking. Such an imbalance of an array of redox-regulated antioxidant
vs. pro-inflammatory genes might, therefore, be associated with the suscept-
ibility or tolerance to disease. It is possible that induction of antioxidant
enzymes may provide initial adaptive or protective responses against oxida-
tive stress and inflammatory mediators. However, during sustained = chronic