RESUMO
BACKGROUND: Inflammation, where vascular endothelial cells are activated by cytokines, recruits circulating leukocytes such as neutrophils into the tissues. Mononuclear phagocytes as well as tissue cells activated by these stimuli produce these chemokines. In this study, the effects of IL-1 and LPS on the expression of CXC chemokines such as GRO-alpha, IL-8 and ENA-78 in vascular endothelial cells and the neutrophil adnesion effects of ENA-78 and GRO-alpha was investigated. METHODS: Human umbilical vein endothelial cells were cultured and stimulated with various concentrations of IL-1 and LPS. The concentrations of the GRO-alpha, IL-8 and ENA-78 secreted were measured using enzyme-linked immunosorbent assay. The effects of ENA-78 and GRO-alpha on neutrophil adhesion to the endothelial cells were also investigated. RESULTS: The addition of IL-1 and LPS to the vascular endothelial cells induced GRO-alpha, IL-8 and ENA-78 secretion in a time- and dose-dependent manner. The neutrophil adhesion was also increased by induction of ENA-78 and GRO-alpha to the vascular endothelial cells in a dose-dependent manner. CONCLUSION: CXC chemokines such as GRO-alpha, IL-8 and ENA-78 secreted by the vascular endothelial cells play an important role in the acute inflammatory responses by stimulating neutrophil adhesion to the vascular endothelial cells, raising the possibility that the CXC chemokines are one of the targets in the clinical application of acute inflammation.
Assuntos
Quimiocinas , Quimiocinas CXC , Citocinas , Células Endoteliais , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana , Inflamação , Interleucina-1 , Interleucina-8 , Leucócitos , Neutrófilos , FagócitosRESUMO
PURPOSE: Kawasaki disease is probably driven by abnormalities of the immune system after infectious insult. In this report, a clinical review with laboratory parameters and the changes of the plasma levels of chemokines(RANTES and Gro-alpha was undertaken according to the clinical stage of Kawasaki disease. METHODS: This investigation included 74 samples from 21 patients(10 boys, 11 girls; mean age, 27.8 months) with Kawasaki disease who met the revised diagnostic guidelines and 5 samples from healthy children. The plasma levels of RANTES and Gro-alpha were measured by enzyme- linked immuno-sorbent assay(ELISA). To analyze the pattern of the gene expression of chemokine mRNA for lymphotactin(Ltn), RANTES, IP-10, MIP-1 beta, MIP-1 alpha MCP-1, IL-8 and I-309 in the peripheral blood monocyte, ribonuclease protection assays(RPA) were performed in 3 patients whose plasma levels of RANTES were very low and not significantly changed after intravenous immunoglobulin(IVIG) treatment. RESULTS: The production of RANTES and Gro-alpha were markedly elevated during the acute and subacute phases of Kawasaki disease compared to those of the normal control. In addition, interestingly, the changing patterns of plasma level of chemokines were not consistent(biphasic) after IVIG treatment. According to the RPA, the expression of RANTES was the most prominent among 8 kinds of chemokines and elevated in all phases of Kawasaki disease. But, there was no ovious relation between clinical characteristics of the disease including the coronary artery dilatation and the level of RANTES. CONCLUSION: These finding suggested that RANTES and Gro-alpha may play an important role in pathophysiology of the Kawasaki disease. Longer follow-up and more case studies will be needed to clearly establish the significance of the changes of RANTES and Gro-alpha in the pathophysiology of Kawasaki disease.