嚴重急性呼吸道症候群的免疫致病機轉(第二年)─(總計畫與子計畫一)SARS病毒及相關蛋白對單核細胞和樹突細胞分泌發炎性細胞激素和趨化激素的影響
Date Issued
2005
Date
2005
Author(s)
江伯倫
DOI
932751B002004Y
Abstract
Objective: To explore the immunopathogenesis of severe acute respiratory distress
syndrome (SARS) and the mechanism of milder disease in young children than in adults.
Method: The SARS-associated coronavirus (SARS-CoV) viral proteins were prepared from
Baculovirus expression system. Peripheral blood mononuclear cells (PBMCs) were
isolated from healthy adult donors by Ficoll-Hypaque density gradient centrifugation.
CD14+ monocytes were purified from PBMCs through MACS column. Then the
monocytes were cultured with IL-4 and GM-CSF to yield dendritic cells. The SARS-CoV
S, N, E, M viral protein were cutltured with monocytes or dendritic cells for 24~48 hrs.
The supernatants were measured for cytokine and chemokine levels by ELISA. Besides,
the pcDNA-S, N, E, M and viral protein were used to stimulate A549 cell line for NF-kB
activation detected by luciferase reporter assay.
Result: The SARS-CoV E protein (500 ng/mL) may induce the secretion of proinflammatory
cytokines (IL-1, IL-6, TNF-α) and chemokine of MCP-1 in human monocytes. The
SARS-CoV N protein might also induce IL-6 and MCP-1 secretion. Dendritic cells
secreted IL-10 and IL-12 cytokines under S protein (1000 ng/mL) stimulation. The
pcDNA-S and pcDNA-N (0.2 μg/mL) or N protein (1 μg/mL) may induce NF-κB
activation in A549 cells.
Conclusion: The SARS-CoV E protein may induce proinflammatory cytokines and
chemokines secretion of moncytes and S protein may induce the release of IL-10 and IL-12
in dendritic cells from healthy adults. Through these cytokines and chemokines, the
immune system may be activated and lead to the cytokine storm and the
immunopathological damage.
Subjects
SARS, dendritic cells, monocyte, NF-kB, A549 cells
SDGs
Publisher
臺北市:國立臺灣大學醫學院臨床醫學研究所
Type
journal article
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