Divergence in intracellular signaling between interleukin-4 (IL-4) and IL-13 in human cells localizes to monomeric/dimeric expression of a transcription factor, the lupus ku autoantigen 70/80, induced by both cytokines

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths. As HCC has a high mortality rate and its incidence is increasing worldwide, understanding and treating HCC are crucial for resolving major public health concerns. In the present study, wound healing screening assays were performed using natural product libraries to identify natural chemicals that can inhibit cancer cell migration. Glaucarubinone (GCB) showed a high potential for inhibiting cell migration. The anti-cancer effects of GCB were evaluated using the HCC cell line, Huh7. GCB showed anti-cancer effects, as verified by wound healing, cell migration, invasion, colony formation, and three-dimensional spheroid invasion assays. In addition, cells treated with GCB showed suppressed matrix metalloproteinase activities. Immunoblotting analyses of intracellular signaling pathways revealed that GCB regulated the levels of Twist1, a crucial transcription factor associated with epithelial-to-mesenchymal transition, and mitogen-activated protein kinase. The invasive ability of cancer cells was found to be decreased by the regulation of Twist1 protein levels. Furthermore, GCB downregulated phosphorylation of extracellular signal-regulated kinase. These results indicate that GCB exhibits anti-metastatic properties in Huh7 cells, suggesting that it could be used to treat HCC.

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Knockdown of transcription factor forkhead box O3 (FOXO3) suppresses erythroid differentiation in human cells and zebrafish

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2015.03.128 ◽

2015 ◽

Vol 460 (4) ◽

pp. 923-930 ◽

Cited By ~ 8

Author(s):

Hai Wang ◽

Yanming Li ◽

Sifeng Wang ◽

Qian Zhang ◽

Jiawen Zheng ◽

...

Keyword(s):

Transcription Factor ◽

Erythroid Differentiation ◽

Human Cells ◽

Forkhead Box

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Attenuation of HIV-1 Replication in Primary Human Cells with a Designed Zinc Finger Transcription Factor

Journal of Biological Chemistry ◽

10.1074/jbc.m400349200 ◽

2004 ◽

Vol 279 (15) ◽

pp. 14509-14519 ◽

Cited By ~ 66

Author(s):

David J. Segal ◽

João Gonçalves ◽

Scott Eberhardy ◽

Christina H. Swan ◽

Bruce E. Torbett ◽

...

Keyword(s):

Transcription Factor ◽

Zinc Finger ◽

Human Cells ◽

Zinc Finger Transcription Factor ◽

Hiv 1 ◽

Primary Human Cells

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Interleukin-4 receptor regulation in human monocytic cells

Blood ◽

10.1182/blood.v84.2.608.608 ◽

1994 ◽

Vol 84 (2) ◽

pp. 608-615 ◽

Cited By ~ 16

Author(s):

H de Wit ◽

DW Hendriks ◽

MR Halie ◽

E Vellenga

Keyword(s):

T Cells ◽

Protein Kinase ◽

Protein Level ◽

Intracellular Signaling ◽

Antigen Expression ◽

Interleukin 4 ◽

Transcriptional Level ◽

Gamma Chain ◽

Monocytic Cells ◽

Interleukin 4 Receptor

Abstract The regulation of the interleukin-4 receptor (IL-4R) was studied at mRNA and protein level in monocytic cells on stimulation with activators of different intracellular signaling pathways and IL-4. Activation of protein kinase C-dependent pathways with phorbol myristate acetate (PMA) or activation of protein kinase A-dependent pathways with DBcAMP and prostaglandin E2 resulted in an augmented IL- 4R expression at mRNA and protein level. Transcriptional and posttranscriptional mechanisms seemed to be involved in the promotive effect of DBcAMP because the transcription rate increased 1.8-fold, and the half-life of IL-4R mRNA was prolonged to 150 minutes compared with 120 minutes in unstimulated cells. In contrast, the effect of PMA could only be ascribed to changes at transcriptional level. However, activation of Ca(2+)-dependent pathways with A23187 or stimulation with IL-4 had no effect on the IL-4R expression. The unresponsiveness to IL- 4 could not be ascribed to a nonfunctional receptor because IL-4 did modulate the CD14, CD23, and HLA-DR antigen expression. These results are in contrast with IL-4R regulation in T cells, which is affected by IL-4- and Ca(2+)-dependent pathways. The discrepancy might be caused by the presence of the common IL-2 receptor gamma chain (gamma c) in T cells and the absence of the gamma c in monocytic cells, as has been shown by polymerase chain reaction. These data indicate that IL-4Rs are differentially regulated, depending on the cell type studied.

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