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Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates
Author(s) -
Remick Daniel G.,
Villarete Lorelie
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.4.471
Subject(s) - nitric oxide , cytokine , reactive oxygen species , reactive nitrogen species , effector , biology , nitric oxide synthase , inflammation , gene expression , biochemistry , immunology , gene , endocrinology
Reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and cytokines are frequent companions at sites of acute inflammation. Previous work has established a clear link between the production of cytokines and the subsequent generation of ROI and RNI. However, more recent data indicates that ROI and RNI not only serve as end‐stage effector molecules of pathogen destruction and tissue injury, but also as initiators of acute inflammation. Specifically, ROI and RNI will up‐regulate cytokine gene expression since antioxidants inhibit interleukin 8 (IL‐8) production and do not decrease production of other cytokines. Treatment with hydroxyl radical scavengers such as dimethyl sulfoxide (DMSO) will decrease the production of IL‐8 in stimulated human whole blood, fibroblasts, type II epithelial cells, and hepatoma cells, 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 (NO)‐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 IL‐8. Our data indicate that ROI and RNI can serve as intracellular second messengers to induce IL‐8 gene expression.