Interleukin-1 β에 의한 Human β-defensin 2의 발현조절기전

Other Titles
Regulation of human β-defensin 2 expression in A549 cells by IL-1 β
Authors
임기조
Issue Date
2004-06
Awarded Date
2004
Abstract
Induction of human β-defensin 2 (HSD-2) by interleukin-1β (IL-1β) in epithelial cells has been reported. However, the mechanism by which IL-1β up-regulates HBD-2 remains poorly understood. In this study, the effect of IL-1β on induction of HBD-2 in A549 cells was investigated. IL-1β markedly increased HBD-2 mRNA expression in concentration-and time-dependent manners. HBD-2 mRNA expression in response to IL-1β was attenuated by pretreatments with GF109203X, Go6976, and staurosporine (inhibitors of protein kinase C (PKC), SB203580 (an inhibitor of p38 mitogen-activated protein kinase (MARK)), SP600125 (an inhibitor of c-Jun N-terminal kinase (JNK)), and LY294002 (an inhibitor of phosphatidylinositol-3-kinase (PI3K), but not PD98053 (an inhibitor of extracellular signal-regulated kinase (ERK)), suggesting involvement of PKC, p38 MAPKs, JNKs, and PI3K in this response. Interestingly, IL-1β induced nuclear factor-𝒌B (NF-𝒌B) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-𝒌B and degradation of inhibitory 𝒌B-α in response to IL-1β stimulation. Importantly, IL-1β induced HBD-2 mRNA expression was inhibited by blockage of NF-𝒌B activation using NF-𝒌B inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1β-induced nuclear translocation of NF-𝒌B was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-𝒌B in response to IL-1β. Together, these results suggest that IL-1β induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-𝒌B transcription factor as well as activation of signaling proteins of PKC, p38 MAPKs, JNKs, and PI3K, but not ERKs.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/11980
Appears in Collections:
3. Thesis (학위논문) > 1. School of Medicine (의과대학) > 석사
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http://dcollection.kmu.ac.kr//jsp/common/DcLoOrgPer.jsp?sItemId=000000003299
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