YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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L1 Cell Adhesion Molecule Suppresses Macrophage-mediated Inflammatory Responses

L1 Cell Adhesion Molecule에 의한 대식세포 매개 염증반응의 억제 기전 분석

  • Yi, Young-Su (Department of Pharmaceutical Engineering, Cheongju University)
  • 이영수 (청주대학교 이공대학 제약공학과)
  • Received : 2016.04.14
  • Accepted : 2016.05.23
  • Published : 2016.06.30
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Abstract

L1 cell adhesion molecule (L1CAM) is a cell surface molecule to initiate a variety of cellular responses through interacting with other cell adhesion molecules in a homophilic or heterophilic manner. Although its expression was found to be upregulated in some tumor cells, including cholangiocarcinomas, and ovarian cancers, and many studies have investigated the role of L1CAM in these cancers, its role in inflammatory responses has been poorly understood. In this study, we explored the role of L1CAM in macrophage-mediated inflammatory responses. L1CAM significantly suppressed the production of nitric oxide (NO), but induced cell proliferation in RAW264.7 cells. L1CAM expression was detectable, but its expression was markedly decreased by lipopolysaccharide (LPS) in RAW264.7 cells. In addition, the expression of pro-inflammatory genes, such as tumor necrosis factor (TNF)-${\alpha}$, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) induced by LPS was dramatically suppressed by L1CAM in RAW264.7 cells. L1CAM inhibited the transcriptional activities of NF-${\kappa}B$ and AP-1 while its cytoplasmic domain deletion form, $L1{\Delta}CD$ did not suppressed their activities in RAW264.7 cells. Moreover, L1CAM suppressed nuclear translocation of p65 and p50 as well as c-Jun, c-Fos and p-ATF2 which are transcription factors of NF-${\kappa}B$ and AP-1, respectively. In conclusion, L1CAM suppressed inflammatory responses in macrophages through inhibiting NF-${\kappa}B$ and AP-1 pathways.

Keywords

References

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