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No. 31 (PI 5)<br />

Impact of interleukin-29 on interferon alpha secretion of plasmacytoid dendritic cell<br />

Chi Hyun Cho, M.D. 1 , Chae Seung Lim, M.D. and Yun Jung Cho, M.D. 1*<br />

1 Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea<br />

Background: The alpha-IFN secretion by plasmacytoid dendritic cell was distinguished by rapid<br />

kinetics, high level (up to 1000 fold higher than most cells), while the plasmacytoid dendritic cells<br />

responded with vigorous alpha-IFN production to stimulation by a variety of viral stimuli and to<br />

synthetic Toll-like receptor agonists. IL-28Rα (type III IFN receptor chain) signaling was demonstrated<br />

not to provide feedback on type I expression in mouse study. In this study, we tried to identify whether<br />

the type III IFN provides feedback or does not do so on alpha-IFN secretion of human plasmacytoid<br />

dendritic cell.<br />

Methods: From eleven healthy donors, 3 ml and 10 ml of whole blood were collected <strong>for</strong> complete<br />

blood cell count by Coulter automatic analyzer and <strong>for</strong> the isolation of peripheral blood mononuclear<br />

cells (PBMC). Plasmacytoid dendritic cell was counted by multiplying % of total PBMC<br />

(flowcytometer) by mononuclear cells of whole blood (Coulter automatic analyzer). PBMC from each<br />

healthy donor was then divided into four groups as follows: group 1- control; group 2- addition of CpG<br />

DNA; group 3- addition of IL-29; group 4- addition of CpG DNA and IL29. Then, the culture media<br />

were incubated <strong>for</strong> 24 hours at 37℃. The supernatants were collected and tested <strong>for</strong> the amount of<br />

IFN-alpha secretion by the flowcytometer.<br />

Results: The number of plasmacytoid dendritic cells (/µL) was 5.29 (±3.05). IFN-alpha (pg/ml)/pDC<br />

(/µL) in each group was as follows: 5.677 (±9.278) in group 1; 1071.546 (±1026.598) in group 2;<br />

14.142 (±21.107) in group 3; 1913.897 (±1525.928) in group 4. There were statistically significant<br />

differences between group 1 vs 2 and group 2 vs 4, whereas there was no statistically significant<br />

difference between group 1 vs 3. The addition of CpG DNA with IL-29 caused human pDC to secret<br />

IFN-alpha about two times more than addition of CpG DNA alone.<br />

Conclusions: Apart from mouse study, one of lambda-IFNs, IL-29 provided feedback on IFN-alpha<br />

expression of human pDC. IL-29 alone did not have impact on IFN-alpha secretion by human pDC, but<br />

with CpG DNA, had synergistic effect on that. Given the knowledge that IL-29 is potential therapeutic<br />

alternatives to type I IFNs in terms of viral infections and tumors, this result could help elucidate the<br />

mechanism of the therapeutic effect by IL-29.<br />

Key Words : CpG DNA, IL-29, IFN-alpha, plasmacytoid dendritic cell<br />

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