Potentiation of Balb/3T3 fibroblast proliferative response by interleukin-1 and epidermal growth factor.
Balb/3T3 fibroblasts respond to interleukin-1 (IL-1) by proliferating in a dose-dependent fashion. Increasing proliferative responses were observed with increasing IL-1 concentration in serum-free medium when the medium was supplemented with insulin, transferrin, and selenium. This response was evident only if the cell culture medium also contained the cyclooxygenase inhibitor indomethacin. When another fibroblast mitogen, epidermal growth factor (EGF) was cocultured with either purified monocyte-derived IL-1 beta or recombinant IL-1 beta, there was a potentiation of proliferation above the expected additive response. Unexpectedly, the response to recombinant IL-1 alpha was only additive with EGF. This suggests that IL-1-mediated activation of synovial fibroblasts in rheumatoid arthritis may be compounded by EGF as well as by other fibroblast mitogens secreted by cells found in the joint. The results further suggest that IL-1 and EGF interactions may play a significant role in wound healing, scarring, and bone resorption. In addition, these results imply that there may be different cellular activation pathways brought to bear in vivo which may depend, in part, on the IL-1 isotype available.
Kimball
E S
ES
Department of Biological Research, Janssen Research Foundation, Spring House, Pennsylvania 19477.
Fisher
M C
MC
Persico
F J
FJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003470:Culture Media; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D005347:Fibroblasts / Q000166:cytology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D012643:Selenium / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology
D003470:Culture Media; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014168:Transferrin; D004815:Epidermal Growth Factor; D012643:Selenium; D007213:Indomethacin