title: Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates.
abstract: 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 upregulate 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Remick
authors.forename: L
authors.initials: L
authors.lastname: Villarete
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide