Tumor necrosis factor is cytotoxic to human fibroblasts in the presence of exogenous arachidonic acid.
Recombinant human tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in serum-free culture medium. However, TNF had a cytotoxic effect upon the growth of FS-4 cells in combination with arachidonic acid. When arachidonic acid was added to culture medium in the absence of TNF, however, it had no effect on the cell growth. Arachidonic acid inhibited the TNF-induced cell growth in a dose-dependent manner: it reversed the TNF-stimulated growth to the control level at a concentration of 10 microM and was cytotoxic to TNF-treated FS-4 cells at higher concentrations. This cytotoxicity of TNF was not observed in FS-4 cells treated with palmitic acid. Indomethacin, a cyclooxygenase inhibitor, decreased the cytotoxic effect that TNF exerted in the presence of arachidonic acid. These results suggest that TNF becomes cytotoxic to FS-4 cells when arachidonic acid present in the culture medium is converted to prostaglandins.
Hori
T
T
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Kashiyama
S
S
Hayakawa
M
M
Shibamoto
S
S
Tsujimoto
M
M
Oku
N
N
Ito
F
F
D001095:Arachidonic Acids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin