PMID- 8488366
OWN - NLM
STAT- MEDLINE
DCOM- 19930609
LR  - 20190814
IS  - 0036-5521 (Print)
IS  - 0036-5521 (Linking)
VI  - 28
IP  - 4
DP  - 1993 Apr
TI  - Tumor necrosis factor-alpha potentiates phospholipase A2-stimulated release and 
      metabolism of arachidonic acid in cultured intestinal epithelial cells (INT 407).
PG  - 323-30
AB  - Tumor necrosis factor-alpha (TNF-alpha), a known pro-inflammatory cytokine, has 
      been suggested to play a role in the pathogenesis of inflammatory bowel disease 
      (IBD) by mediating damage to the intestinal epithelial cells. The present study 
      demonstrates that TNF-alpha potentiates release and metabolism of 14C-labeled 
      arachidonic acid (14C-AA) in cultured intestinal epithelial cells (INT 407). 
      Although TNF-alpha on its own was but a weak stimulator of cellular 14C-AA 
      turnover, it significantly potentiated the release of 14C-AA and 14C-labeled 
      prostaglandin E2(14C-PGE2) after stimulation with three known phospholipase A2 
      activators: phospholipase. C from Clostridium perfringens, the calcium ionophore 
      A23187, and the phorbol ester 4-beta-phorbol-12-myristate-13-acetate (PMA). The 
      phospholipase A2 inhibitor quinacrine significantly reduced both AA and PGE2 
      release after combined stimulation with phospholipase C and TNF-alpha. In 
      contrast to its effect on the AA turnover, TNF-alpha did not affect the 
      phospholipase C-stimulated production of platelet-activating factor 
      (PAF-acether). Taken together, these findings indicate that a) TNF-alpha 
      potentiates phospholipase A2-stimulated AA release from cultured intestinal 
      epithelial cells; b) TNF-alpha may stimulate phospholipase A2-dependent AA 
      release without affecting the formation of PAF-acether and c) pretreatment with 
      TNF-alpha potentiates the formation of PGE2 after stimulation with phospholipase 
      A2 activators. In summary, the present investigation points to the possibility 
      that TNF-alpha may stimulate intestinal epithelial cells to produce biologically 
      active AA metabolites and that this stimulation may be modulated by components of 
      the intestinal luminal content, like bacterial toxins.
FAU - Gustafson-Svard, C
AU  - Gustafson-Svard C
AD  - Dept. of Occupational Medicine, Faculty of Health Sciences, Linkoping University, 
      Sweden.
FAU - Tagesson, C
AU  - Tagesson C
FAU - Boll, R M
AU  - Boll RM
FAU - Kald, B
AU  - Kald B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Gastroenterol
JT  - Scandinavian journal of gastroenterology
JID - 0060105
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 37H9VM9WZL (Calcimycin)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Arachidonic Acid/*metabolism
MH  - Calcimycin/pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Dinoprostone/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Epithelium/metabolism
MH  - Humans
MH  - Intestinal Mucosa/*metabolism
MH  - Lipid Metabolism
MH  - Phospholipases A/*pharmacology
MH  - Phospholipases A2
MH  - Platelet Activating Factor/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Type C Phospholipases/pharmacology
EDAT- 1993/04/01 00:00
MHDA- 1993/04/01 00:01
CRDT- 1993/04/01 00:00
PHST- 1993/04/01 00:00 [pubmed]
PHST- 1993/04/01 00:01 [medline]
PHST- 1993/04/01 00:00 [entrez]
AID - 10.3109/00365529309090250 [doi]
PST - ppublish
SO  - Scand J Gastroenterol. 1993 Apr;28(4):323-30. doi: 10.3109/00365529309090250.