Induction and localization of NOD2 protein in human endothelial cells.
NOD2 is mainly expressed in human monocytes/macrophages and intestinal epithelial cells and has been speculated to play in gut physiology. However, whether NOD2 is expressed in vascular endothelium is not currently determined. Human umbilical vascular endothelial cells (HUVECs) minimally expressed NOD2 gene, whereas stimulation of HUVEC with bacterial LPS, IL-1beta, or TNF-alpha resulted in significant up-regulation of NOD2. NOD2 protein was mostly localized in the cytoplasm. Overexpression of wild-type NOD2 (WT-NOD2) gene induced NF-kappaB-dependent transcriptional activity and this activity was further increased by muramyl dipeptide (MDP). Otherwise, down-regulation of WT-NOD2 gene by antisense NOD2 abolished NF-kappaB-dependent transcriptional activity mediated by either WT-NOD2 itself or MDP. Since vascular endothelial cells, like macrophages and epithelial cells, are critical targets for the circulating bacterial molecules such as MDP, collectively, the results presented here suggest that NOD2 may play an important role in recognizing structural patterns of bacterial pathogen in the endothelium.
Oh
Hyun-Mee
HM
Department of Physiology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Lee
Hyun-Ju
HJ
Seo
Geom-Seog
GS
Choi
Eun-Young
EY
Kweon
Seok-Hyun
SH
Chun
Churl-Hong
CH
Han
Weon-Cheol
WC
Lee
Kang-Min
KM
Lee
Myeung-Su
MS
Choi
Suck-Chei
SC
Jun
Chang-Duk
CD
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine