Pentoxifylline inhibits tumor necrosis factor-alpha induced synthesis of complement component C3 in human endothelial cells.
Vascular endothelium is a major target for the inflammatory damage that occurs with multiple organ dysfunction associated with sepsis and other trauma. The growing appreciation of endothelium as a target of inflammation has obscured the importance of these cells as a source of inflammatory mediators. In the following study we evaluated the ability of tumor necrosis factor-alpha (TNF) to induce the synthesis of complement component C3 in human umbilical vein endothelial cells (HUVEC) and whether pentoxifylline (PTX) could reduce C3 expression. Confluent monolayers of HUVEC were treated with increasing concentrations of TNF with and without two concentrations of PTX. Concentrations of C3 were determined every 48 h for 144 h in cellular supernatants and C3 mRNA was amplified using RT-PCR. TNF increased C3 release from HUVEC in a concentration dependent manner. PTX added at the same time as TNF significantly reduced C3 release at the 96 h time point. Consistent with data on C3 release PTX inhibited the increased C3 mRNA expression associated with TNF treatment. TNF increases C3 synthesis and release from endothelial cells which were inhibited by clinical concentrations of PTX. This data further supports the potential benefit of PTX in multiple organ dysfunction and other inflammatory processes involving the endothelium by inhibiting one of the major mediators of vascular damage.
Hoie
Eric Brian
EB
College of Pharmacya, University of Nebraska Medical Center, Omaha 68198-6045, USA.
McGuire
Timothy Robert
TR
Leuschen
Patricia Mary
PM
Zach
Terrence Leo
TL
D002478:Cells, Cultured; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010431:Pentoxifylline / Q000494:pharmacology*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D003176:Complement C3; D011498:Protein Precursors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline