Phospholipase A2 is activated by tumor necrosis factor-alpha in primary hepatocytes stimulated by a deleted form of hepatocyte growth factor.
Several factors are released in the liver microenvironment immediately after injury. Among these factors TNF alpha is implicated as a regulator of hepatocyte proliferation. Hepatocytes in the intact liver are mostly in the G0 phase of the cell cycle and after injury (including collagenase perfusion) display a constitutive expression of the growth-regulated c-myc oncogene. TNF alpha co-added with dHGF in hepatocyte cultures, superinduced the DNA synthetic response observed at all time points. In parallel, TNF alpha/dHGF-treated hepatocytes have shown increased expression of the c-myc oncogene at times corresponding to the in vitro G1 phase of the cell cycle. TNF alpha activated PLA2 in hepatocytes and it is believed that the subsequent production of PGE2 plays a role in the "priming" process in these cells and at the same time amplifies the proliferating signals induced by hepatocyte-specific growth factors.
Georgakopoulos
E
E
2nd Department of Physiology, University of Heidelberg, Germany.
McMenamin
M
M
Skouteris
G G
GG
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D007213:Indomethacin