Dg. Remick et L. Villarete, REGULATION OF CYTOKINE GENE-EXPRESSION BY REACTIVE OXYGEN AND REACTIVE NITROGEN INTERMEDIATES, Journal of leukocyte biology, 59(4), 1996, pp. 471-475
Reactive oxygen intermediates (ROI), reactive nitrogen intermediates (
RNI), and cytokines are frequent companions at sites of acute inflamma
tion. Previous work has established a clear link between the productio
n of cytokines and the subsequent generation of ROI and RNI. However,
more recent data indicates that ROI and RNI not only serve as end-stag
e effector molecules of pathogen destruction and tissue injury, but al
so as initiators of acute inflammation. Specifically, ROI and RNI will
upregulate cytokine gene expression since antioxidants inhibit interl
eukin 8 (IL-8) production and do not decrease production of other cyto
kines. Treatment with hydroxyl radical scavengers such as dimethyl sul
foxide (DMSO) will decrease the production of IL-8 in stimulated human
whole blood, fibroblasts, type II epithelial cells, and hepatoma cell
s, but not other cytokines. Addition of exogenous ROI will increase IL
-8 production in these same cells, Inhibition of nitric oxide synthase
will decrease production of IL-8, whereas addition of nitric oxide (N
O)-generating compounds will increase production of IL-8. The hydroxyl
radical appears to be the final common pathway of cell activation for
IL-8 synthesis, since DMSO will inhibit the NO-driven production of I
L-8. Our data indicate that ROI and RNI can serve as intracellular sec
ond messengers to induce IL-8 gene expression.