Down-regulation of macrophage transforming growth factor-beta messenger RNA expression by IL-7.
Transforming growth factor-beta (TGF-beta) is a potent inhibitor of immune responses. Macrophage-derived products, including TGF-beta, have been suggested as inhibitors of the antitumor immune response. We hypothesized that IL-7, a cytokine with antitumor properties, may exert its immunoregulatory effects in part through the down-regulation of TGF-beta. To test this hypothesis we analyzed IL-2-stimulated murine macrophage TGF-beta mRNA expression following exposure to IL-7 both in vitro and in vivo. IL-7 down-regulated IL-2-induced TGF-beta expression by macrophages in vitro, as well as after i.p. injections of IL-2 and IL-7 in vivo. The IL-7-mediated inhibition of TGF-beta mRNA expression did not require new protein synthesis and therefore appears to be a direct effect of IL-7. IL-7 had no significant effect on the stability of TGF-beta mRNA. Nuclear run-on assays revealed that the suppression of IL-2-induced TGF-beta gene expression by IL-7 is mediated at the level of transcription. Also, IL-7 decreased TGF-beta secretion as measured by bioassay. We conclude that IL-7 down-regulates TGF-beta and suggest that some of the proliferative and cytolytic activities mediated by cells exposed to IL-7 may be caused by a decrement in macrophage-derived TGF-beta.
Dubinett
S M
SM
Department of Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Medicine.
Huang
M
M
Dhanani
S
S
Wang
J
J
Beroiza
T
T
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*
D007376:Interleukin-2; D015851:Interleukin-7; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta