Divergent cell-specific effects of activin-A on thymocyte proliferation stimulated by phytohemagglutinin, and interleukin 1beta or interleukin 6 in vitro.
Activin-A is a member of the transforming growth factor-beta (TGF-beta) cytokine family. Based on studies in several cell systems, activin-A has been postulated to be a specific inhibitor of the actions of the inflammatory cytokine, interleukin 6. In cultures of adult rat thymocytes, activin-A inhibited sub-optimal phytohemagglutinin-induced and interleukin 1beta-stimulated proliferation, as measured by [(3)H]-thymidine incorporation in vitro. In contrast with TGF-beta1, which exerted similar inhibitory effects on thymocyte proliferation, activin-A activity was reduced by increasing the concentration of phytohemagglutinin or addition of the reducing agent, beta-mercaptoethanol. Both activin-A and TGF-beta1 inhibited the in vitro production of interleukin 6 by thymocytes in the presence of phytohemagglutinin and interleukin 1beta. In the presence of exogenous interleukin 6, however, both activin-A and TGF-beta1 stimulated thymocyte proliferation. These data suggest that activin-A inhibits thymocyte growth and differentiation, at least in part, by inhibiting endogenous production of interleukin 6, but stimulates thymocyte growth when exogenous interleukin 6 is present in vitro. These data indicate that activin interacts with other cytokines to exert complex regulation of T cell development, and is not an inhibitor of interleukin 6 action in all cell systems.
Hedger
M P
MP
Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, 3168, Australia. mark.hedger@med.monash.edu.au
Phillips
D J
DJ
de Kretser
D M
DM
D028341:Activins; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology* / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D008623:Mercaptoethanol