Characteristics of human synovial fibroblast activation by IL-1 beta and TNF alpha.
Human synovial fibroblast cell lines (HSN), established from tissues obtained from the knee joints of arthritis patients undergoing arthoplasty, were used to investigate the effects of human interleukin-1 (IL-1) beta and tumour necrosis factor (TNF)alpha on proliferation and prostaglandin E2 (PGE2) secretion. IL-1 beta and TNF alpha were equipotent stimulators of HSN proliferation. Classical non-steroidal anti-inflammatory drugs and glucocorticoids significantly augmented this effect. In addition, IL-1 beta and TNF alpha were potent inducers of PGE2 production while exogenous PGE2 was growth inhibiting. These data suggest that the secretion of PGE2 by monokine-stimulated HSN exerts a negative feedback signal. Further examination of IL-1 beta- and TNF alpha-induced PGE2 secretion revealed IL-1 beta to be a more potent stimulator; however, this observation may be due, in part, to differences in the kinetics of induction. Rabbit anti-IL-1 beta and anti-TNF alpha specifically neutralized both proliferation and PGE2 production induced by these monokines, but anti-IL-1 beta (or anti-IL-1 alpha) did not block TNF alpha activity. It is unclear whether TNF alpha stimulates HSN to produce IL-1, but the antibody data suggest that extracellular IL-1 is not responsible for TNF alpha in vitro activity.
Gitter
B D
BD
Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285.
Labus
J M
JM
Lees
S L
SL
Scheetz
M E
ME
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone