Involvement of prostaglandin-producing pathway in the cytotoxic action of tumor necrosis factor.

Abstract:

:To elucidate the cytotoxic mechanism of tumor necrosis factor (TNF), we isolated TNF-resistant sublines of L929 cells. As compared with L929 cells, TNF-resistant cells retained similar number and affinity of TNF-binding sites, and showed a similar growth rate. TNF stimulated arachidonate release from L929 cells, while no stimulation was observed at all in TNF-resistant cells tested. The cytotoxic action of TNF on L929 cells was inhibited by indomethacin, suggesting that prostaglandin may be involved in the action. Therefore, TNF-stimulated prostaglandin production was examined in L929 and TNF-resistant sublines. The amount of PGE2 produced by L929 cells was increased more than 5-fold after the addition of TNF, whereas the amount of PGE2 did not change in the resistant sublines following addition of the factor. TNF-stimulated arachidonate release and PGE2 production were reversed by islet-activating protein (IAP)-treatment of L929 cells. These results suggest that arachidonate release and subsequent prostaglandin production are important for the cytotoxic action of TNF and that these processes are mediated by GTP-binding protein (G protein) that is coupled to the TNF-receptor.

journal_name

Cell Struct Funct

authors

Hayakawa M,Oku N,Takagi T,Hori T,Shibamoto S,Yamanaka Y,Takeuchi K,Tsujimoto M,Ito F

doi

10.1247/csf.16.333

subject

Has Abstract

pub_date

1991-08-01 00:00:00

pages

333-40

issue

4

eissn

0386-7196

issn

1347-3700

journal_volume

16

pub_type

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