| Interleukin-8 (IL-8), a member of the CXC chemokine family, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. It have been associated with a number of acute and chronic inflammatory diseases and conditions, including asthma, rheumatoid arthritis, sepsis, inflammatory bowel disease, and adult respiratory distress syndrome. IL-8 is secreted in a stimulus-specific manner by a wide variety of cell types and is regulated primarily at the level of gene transcription.IL-8 exhibits multiple activities on neutrophils, such as induced shape change, lysosomal enzyme release, induction of respiratory burst, generation of superoxide and hydrogen peroxide from neutrophil, expression of adhesion molecules on neutrophils to unstimulated endothelial cells. IL-8 plays important roles in host defense by recruiting specific subsets of leukocytes to sites of inflammation and injury. IL-8 can be pre-induced massively and pro-inflammatory and rapidly in vitro by various types of cells in response to inflammatory stimuli such as lipopolysacchride (LPS) and correlative pro-inflammatory cytokines. Various animal models of inflammation have established IL-8 as a principle chemotactic factor directing neutrophil recruitment to and activation at the inflammatory focus.IL-8 is produced by several cell types, including neutrophils, perpheral blood monocytes, tissue macrophages, fibriblasts, endothelial cells, epithelial cells, T lymphocytes, hepatocytes, and synovial cells. Numerous exogenous and endogenous stimuli such as endotoxin (LPS), stresses, viruses, and bacteria as well as PHA, IL-1β, TNFα, PMA, fMLP, and A23187 promote IL-8 gene activation. Neutrophil themselves have been shown to release IL-8 in response to various stimuli such as LPS. IL-8 action is mediated through a large super-family of seven transmembrane spanning G- protein coupled receptors.In this paper, a series of stimuli such as LPS, PMA, A23187, and fMLP were studied to investigate their actions on IL-8 biosynthesis in HL-60 cells then established the model of IL-8 production. The actions were also observed in U937 cells as well as in human knee synovial cells.About 60 compounds were studied to investigate their effects on IL-8 biosynthesis in this model. It was found 10 compounds have inhibitory effects on IL-8 production. Then three compounds Vam3, Vam4 and Vam21 were chosen from those effective compounds selected to study their actions further. It was found that Vam3, Vam4 and Vam21 have significant inhibitory effects on IL-8 biosynthesis induced with LPS 5μg·ml-1 and the IC50 was 2.0×10-10 mol·L-1, 1.9×10-9 mol·L-1 and 2.2×10-8 mol·L-1, respectively. The IC50 of Iso was 2.2×10-8mol·L-1. It was also found that Aspirin, Salisycride, and hydrocortison have the obvious inhibitory effects on IL-8 secretion with the inhibition of 86.2%, 82.7% and 136.3%, respectively.Compound Vam3 has obviously inhibitory effect on IL-8 production induced with LPS in U937 cells with the IC50 of 4.5×107mol·L-1. Isorhapotigenin (Iso) could significantly reduce IL-8 secretion induced with TNFα 0.25U·ml-1- in HSC with the IC50 of 8.0×10-6mol·L-1 and the inhibition of Vam3, Vam4 and Vam21 at concentration of 2.0×l0-6mol·L-1 was 57.2%, 50.8% and 25.1% respectively. The...
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