Characterization of constitutive and inducible transcription factors binding to the P2 NF-AT site in the human interleukin-4 promoter

Li‐Weber, Min; Salgame, Padmini; Hu, Chenggang; Krammer, Peter H.

doi:10.1016/s0378-1119(96)00820-7

Cited by 22 publications

(14 citation statements)

References 27 publications

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“…For example, c-fos has been shown to bind to the P2 NFAT element in the IL-4 promoter in T cells (31). In addition, c-fos has been shown to strongly activate transcription of a multimerized NFAT/AP-1 site from the IL-4 promoter (32).…”

Section: Discussionmentioning

confidence: 99%

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A Role for Caspases in Controlling IL-4 Expression in T Cells

Sehra

Patel

Kusam

et al. 2005

The Journal of Immunology

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Although caspase activation is critical for T cell proliferation following activation, the role of caspases in T cell differentiation is unclear. In this study, we have examined the effect of inhibition of caspases on the process of Th1/Th2 differentiation. Naive CD4+ T cells activated under neutral differentiation conditions in the presence of the pan caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (Z-VAD) fluoromethylketone showed increased Th2 cell differentiation concomitant with an up-regulation of GATA-3. Z-VAD induced optimal Th2 differentiation when T cells were stimulated under strong primary activation conditions. Treatment of naive CD4+ T cells with Z-VAD under strong activation conditions led to a 6-fold increase in IL-4 mRNA compared with control-treated T cells. The Z-VAD-induced increase in IL-4 transcription occurred within 24 h of activation and was independent of Stat6. IFN-γ mRNA expression was not affected by Z-VAD at the 24-h time point. Z-VAD did not augment IL-4 expression from a committed Th2 cell, suggesting that caspases regulate IL-4 expression specifically during primary T cell activation. Z-VAD did not augment IL-12-driven Th1 differentiation. Activation of T cells in the presence of Z-VAD led to a specific increase in the expression of the transcription factor c-fos. Lastly, retrovirus-mediated expression of the antiapoptotic protein Bcl-2 resulted in an enhancement of Th2 cytokine expression, suggesting that inhibition of caspase activation by Bcl-2 can also modulate IL-4 expression. These findings reveal a novel regulatory mechanism of cytokine expression by caspases, and may explain how signaling pathways that inhibit apoptosis tend to promote Th2 differentiation.

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Section: Discussionmentioning

confidence: 99%

“…10). Because c-fos has been connected to IL-4 transcription (31,32), and AP-1 factors in general are strongly implicated in IL-4 transcription (33,34), the up-regulation of c-fos after Z-VAD treatment may be responsible for the increased IL-4 expression also observed with Z-VAD.…”

Section: Caspase Inhibition Leads To An Increase In C-fos Expression mentioning

confidence: 99%

A Role for Caspases in Controlling IL-4 Expression in T Cells

Sehra

Patel

Kusam

et al. 2005

The Journal of Immunology

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“…Nonetheless, the human P2 element also supports the binding of NFAT and AP-1 using T cell nuclear extracts in EMSA. 35 We analyzed the ability of nuclear proteins isolated from Jurkat cells to interact with a 30-bp oligonucleotide spanning the −175 to −146 Leukemia region in EMSA. As shown in Figure 3, six complexes formed on this oligonucleotide using nuclear extracts obtained from calcium ionophore activated cells.…”

Section: Several Nuclear Factors Bind the P2 Element In Electrophoretmentioning

confidence: 99%

Characterization of a novel negative regulatory element in the human interleukin 4 promoter

et al. 2000

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“…Besides PRE-I and P1, the IL-4 promoter also contains several composite sites that bind AP-1 and NF-AT cooperatively (31,45). Activation of T cells by ␣-CD28 has been shown to strongly induce AP-1 transcriptional activity via posttranslational modification (37).…”

Section: Figmentioning

confidence: 99%