The activation of human fibroblast prostaglandin E production by interleukin 1.
We have examined the induction of prostaglandin E2 (PGE2) release from fibroblasts by human interleukin 1 (IL-1). A number of fibroblast cell lines appear to respond to IL-1 in a fashion similar to that seen with synovial fibroblast cultures. Using the Gin-1 primary fibroblast cell line, the earliest time where a significant increase in PGE2 release can be detected is 2 hr. Thereafter PGE2 appears to increase dramatically, with levels after 5 hr increased over 50-fold above baseline. IL-1 appears to directly induce the increase in PGE2 since removal of other proteins from culture medium does not affect induction. PGE2 induction by IL-1 also does not require cell proliferation. The induction appears to involve the synthesis of new protein since the enhanced release can be completely blocked by addition of actinomycin D or cycloheximide. Arachidonic acid mobilization in cells does not appear to be altered following IL-1 addition. However, the ability to convert arachidonic acid to PGE2 is increased following 5 hr of culture with IL-1. While increasing the release of PGE2, the addition of phorbol esters, alone or in combination with calcium ionophores, does not mimic the protein synthesis-dependent increase seen with IL-1. Taken together these results suggest that IL-1 induction of fibroblast PGE2 involves the synthesis of new protein or proteins involved in the conversion of free arachidonic acid to PGE2.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015759:Ionomycin; D011458:Prostaglandins E / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000502:physiology; D017472:Receptors, Interleukin-1; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014357:Trypsin
D001095:Arachidonic Acids; D004987:Ethers; D007375:Interleukin-1; D011458:Prostaglandins E; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003609:Dactinomycin; D016718:Arachidonic Acid; D015759:Ionomycin; D003513:Cycloheximide; D014357:Trypsin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin