Modulation of transforming growth factor beta-1 gene expression by interleukin-12.
The interaction of cytokines and their net balance with regard to macrophage activation (or deactivation) and immune stimulation (or suppression), ultimately determines the success of host-immune response at sites of active infection. A regulatory role for interleukin (IL)-12 in production of transforming growth factor (TGF)-beta1 has been suggested, however, remains controversial. In this study, we analyzed the effect of IL-12 on TGF-beta1 expression in the human lines, K562 and A549, and in primary human monocytes and macrophages. We found that IL-12 down-regulates TGF-beta1 mRNA expression in K562, monocytes and bone marrow cells, and to a lesser extent in the A549 cells. Using constructs containing different regions of the first promoter of the TGF-beta1 gene and a reporter gene, we also demonstrate that this effect is mediated through the TGF-beta1 gene promoter in the K562 and monocytic cell types. In conclusion, the critical role of IL-12 in the early activation of the immune response to pathogens may include down-modulation of TGF-beta1 gene activity.
Wilkinson
K A
KA
Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio 44106-4984, USA.
Aung
H
H
Wu
M
M
Toossi
Z
Z
D019898:Autocrine Communication; D001854:Bone Marrow Cells / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12