Transcriptional up-regulation of the signaling regulatory protein LNK in activated endothelial cells.
BACKGROUND
A better understanding of inflammatory processes in endothelial cells (ECs) might reveal new ways of controlling inflammation and graft rejection. This study investigates EC genes regulated in response to human tumor necrosis factor (TNF)-alpha and xenogeneic natural antibodies (XNAs) that contribute to endothelial activation during transplantation.


METHODS
Gene expression between resting and activated ECs was investigated by RNA differential display reverse-transcriptase polymerase chain reaction and confirmed by reverse-Northern blot.


RESULTS
Forty-five cDNA fragments corresponding to genes up-regulated in activated ECs were identified. Our findings show that TNF-alpha-mediated EC activation was associated with increased levels of mRNA for the adaptor protein Lnk, the nuclear protein RED, and the initiation factor eIF4G. We further show that Lnk and eIF4G were also up-regulated in response to XNA binding to ECs.


CONCLUSIONS
Our data suggest that TNF-alpha and XNAs could share common signaling pathways involving Lnk and eIF4G but may also drive specific transcriptional events.
Boulday
Gwénola
G
INSERM U437 Immunointervention en Allo-Xénotransplantation and Institut de Transplantation et de Recherche en Transplantation, C.H.U. Hôtel-Dieu, Nantes Cedex, France.
Coulon
Flora
F
Fraser
Christopher C
CC
Soulillou
Jean-Paul
JP
Charreau
Béatrice
B
D048868:Adaptor Proteins, Signal Transducing; D000910:Antibodies, Heterophile / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D000910:Antibodies, Heterophile; D016207:Cytokines; D039603:Eukaryotic Initiation Factor-4G; C090444:IK protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; C490778:SH2B3 protein, human; D014409:Tumor Necrosis Factor-alpha