CREB, ATF, and AP-1 Transcription Factors Regulate IFN-γ Secretion by Human T Cells in Response to Mycobacterial Antigen

Samten, Buka; Townsend, John C.; Weis, Steven E.; Bhoumik, Anindita; Klucar, Peter; Shams, Homayoun; Barnes, Peter F.

doi:10.4049/jimmunol.181.3.2056

Cited by 76 publications

(67 citation statements)

References 46 publications

(64 reference statements)

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“…We have shown previously that the transcription factors cyclic AMP response element binding protein (CREB), activating transcription factor w (ATF-2), and c-Jun bind to the IFN-␥ proximal promoter and upregulate IFN-␥ production by T cells (37,38). The phosphorylation of these transcription factors increases their binding to the transcriptional complex.…”

Section: Resultsmentioning

confidence: 99%

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Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

et al. 2011

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Smoking is associated with increased susceptibility to tuberculosis and influenza. However, little information is available on the mechanisms underlying this increased susceptibility. Mice were left unexposed or were exposed to cigarette smoke and then infected with Mycobacterium tuberculosis by aerosol or influenza A by intranasal infection. Some mice were given a DNA vaccine encoding an immunogenic M. tuberculosis protein.Gamma interferon (IFN-␥) production by T cells from the lungs and spleens was measured. Cigarette smoke exposure inhibited the lung T-cell production of IFN-␥ during stimulation in vitro with anti-CD3, after vaccination with a construct expressing an immunogenic mycobacterial protein, and during infection with M. tuberculosis and influenza A virus in vivo. Reduced IFN-␥ production was mediated through the decreased phosphorylation of transcription factors that positively regulate IFN-␥ expression. Cigarette smoke exposure increased the bacterial burden in mice infected with M. tuberculosis and increased weight loss and mortality in mice infected with influenza virus. This study provides the first demonstration that cigarette smoke exposure directly inhibits the pulmonary T-cell response to M. tuberculosis and influenza virus in a physiologically relevant animal model, increasing susceptibility to both pathogens.

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Section: Resultsmentioning

confidence: 99%

“…Whole-cell protein extracts of T cells from lungs and spleens were prepared as described previously (36)(37)(38) and were quantified by bicinchoninic acid assay (Pierce Biotechnology). SDS-PAGE and Western blotting were performed as previously described (36).…”

Section: Methodsmentioning

confidence: 99%

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

et al. 2011

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“…JUN is a known positive regulator of IFNG gene expression (62,63). JUN is able to form heterodimers with ATF2 that have been shown to bind and transactivate the IFNG promoter (49,62,63). As JUN was also upregulated by IL-12 and IL-12 plus IL-18 in our microarray analysis, we hypothesized that ATF3 may form an activating complex with JUN and thereby induce IFN-g production.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a recent report described ATF2 as a positive regulator of JUN expression in human T cells (49). Thus, we examined the effect of ATF3 knockdown on JUN expression also and discovered that the ATF3 knockdown resulted in decreased expression of JUN (Fig.…”

Section: Atf3 Is a Positive Regulator Of Ifn-g Production And T-bet Amentioning

confidence: 99%

Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression

Filén

Ylikoski

Tripathi

et al. 2010

The Journal of Immunology

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IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-α in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-α, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4+ Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-α, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4+ T cells enhanced the production of IFN-γ, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-γ production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4+ T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation.

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“…However, the cell production of the majority of anti-angiogenic proteins was strongly inhibited by SIM treatment in the presence of CoCl 2 (Table II). This effect may be associated with the suppressive effects of SIM exerted on other transcription factors (such as activator protein-1) that control the expression of the genes encoding for these proteins (38,39). Since there is a tight correlation between HIF-1α expression and oxidative stress intensity (40,41), and a large body of data demonstrated the role of SIM in the modulation of tumor oxidative stress (1,42,43), the current study assessed a general marker for tumor oxidative stress, MDA.…”

Section: Discussionmentioning

confidence: 99%

HIF-1α acts as a molecular target for simvastatin cytotoxicity in B16.F10 melanoma cells cultured under chemically induced hypoxia

et al. 2017

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Abstract. Our previous studies reported that one of the main mechanisms of the antitumor activity of simvastatin (SIM) in B16.F10 murine melanoma cells was associated with strong suppression of the constitutive cell production of the α subunit of the heterodimeric transcription factor hypoxia-inducible factor (HIF)-1. Thus, the present study aimed to broaden this finding under hypoxic conditions induced by incubation of B16.F10 cells with cobalt chloride, when the constitutive production of HIF-1α in these melanoma cells is amplified by inducible expression of this factor. The data demonstrated that the SIM antiproliferative effects on melanoma cells were mediated mainly via strong suppressive actions on the B16.F10 cell capacity to support tumor angiogenesis and inflammation, as a result of a high inhibition of the inducible expression of HIF-1α. However, the constitutive expression of HIF-1α was not affected by SIM, probably due to the lack of effect of this statin on nuclear factor-κB production in B16. F10 cancer cells at the concentration tested. Additionally, the present study noted slight reducing effects of SIM on tumor oxidative stress, which may contribute to the main inhibitory action of this statin on HIF-1α production in hypoxic tumor cells. Collectively, these data are valuable for future anticancer strategies based on SIM administration in combination with cytotoxic drugs that are able to counteract the constitutive expression of HIF-1α in tumors.

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CREB, ATF, and AP-1 Transcription Factors Regulate IFN-γ Secretion by Human T Cells in Response to Mycobacterial Antigen

Cited by 76 publications

References 46 publications

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis

Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression

HIF-1α acts as a molecular target for simvastatin cytotoxicity in B16.F10 melanoma cells cultured under chemically induced hypoxia

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