Effects of transforming growth factor-beta on bone marrow macrophage Ia expression induced by cytokines.
The initiation of the immune response is regulated, in part, by the effect of cytokines on the level of expression of major histocompatibility complex (MHC) class II antigens on antigen-presenting cells (APC). The expression of class II antigens on B cell and macrophage APC is induced by IFN-gamma and IL-4, and GM-CSF induces class II expression on macrophages (M phi). Our results show that transforming growth factor-beta (TGF-beta) inhibits IL-4- and GM-CSF-induced Ia gene expression on bone marrow macrophages but enhances IFN-gamma-induced gene expression. Nuclear run-on experiments demonstrated that the inhibitory effects of TGF-beta on GM-CSF- and IL-4-induced Ia antigen expression were primarily posttranscriptional and augmentation of IFN-gamma by TGF-beta was largely transcriptionally regulated.
Gollnick
S O
SO
Department of Molecular Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cheng
H L
HL
Grande
C C
CC
Thompson
D
D
Tomasi
T B
TB
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor