Inhibition of interferon-γ signaling by a mercurio-substituted dihydropsoralen in murine keratinocytes

Martey, Christine A.; Vetrano, Anna M.; Whittemore, Marilyn S.; Mariano, Thomas M.; Heck, Diane E.; Laskin, Debra L.; Heindel, Ned D.; Laskin, Jeffrey D.

doi:10.1016/j.bcp.2005.10.001

Cited by 5 publications

(6 citation statements)

References 27 publications

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“…Coinciding with the production of reactive nitrogen species is the depletion of l ‐arginine mediated by production of ArgI 6,15,64–67 . The Nos2 is inducible by IFN‐γ expression regardless of whether it is from intracellular production or extracellular sources 68,69 . To define whether internal changes in Nos2 and IFN‐γ play a role in these cells, RNA was extracted and mRNA levels were analysed using RT‐PCR.…”

Section: Resultsmentioning

confidence: 99%

“…6,15,[64][65][66][67] The Nos2 is inducible by IFN-c expression regardless of whether it is from intracellular production or extracellular sources. 68,69 To define whether internal changes in Nos2 and IFN-c play a role in these cells, RNA was extracted and mRNA levels were analysed using RT-PCR. Expression of ArgI, Nos2 and IFN-c were increased in MDSC regardless of tissue type.…”

Section: Il-12 Treatment Reduces the Expression Of Argi Nos2 And Ifnmentioning

confidence: 99%

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The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis

et al. 2011

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Summary Myeloid‐derived suppressor cells (MDSC) are important to the tumour microenvironment as they actively suppress the immune system and promote tumour progression and metastasis. These cells block T‐cell activation in the tumour microenvironment, preventing anti‐tumour immune activity. The ability of a treatment to alter the suppressive function of these cells and promote an immune response is essential to enhancing overall therapeutic efficacy. Interleukin‐12 (IL‐12) has the potential not only to promote anti‐tumour immune responses but also to block the activity of cells capable of immune suppression. This paper identifies a novel role for IL‐12 as a modulator of MDSC activity, with implications for IL‐12 as a therapeutic agent. Treatment with IL‐12 was found to alter the suppressive function of MDSC by fundamentally altering the cells. Interleukin‐12‐treated MDSC exhibited up‐regulation of surface markers indicative of mature cells as well as decreases in nitric oxide synthase and interferon‐γ mRNA both in vitro and in vivo. Treatment with IL‐12 was also found to have significant therapeutic benefit by decreasing the percentage of MDSC in the tumour microenvironment and increasing the percentage of active CD8+ T cells. Treatment with IL‐12 resulted in an increase in overall survival accompanied by a reduction in metastasis. The findings in this paper identify IL‐12 as a modulator of immune suppression with significant potential as a therapeutic agent for metastatic breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Il-12 Treatment Reduces the Expression Of Argi Nos2 And Ifnmentioning

confidence: 99%

The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis

et al. 2011

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“…Although the Sema3A promoter has not yet been investigated, the NGF promoter contains an AP-1 element important for the NGF transcriptional activity [33,34]. The psoralen functions by interfering with AP-1 in murine keratinocytes, and thereby inhibits the DNA binding of AP-1 [35]. Other groups have reported that the chromatin structure in human epithelial cells is affected by PUVA [36,37], and the changes in chromatin structure influence the DNA binding activity of transcription factors [32].…”

Section: Discussionmentioning

confidence: 96%

Psoralen-ultraviolet A therapy alters epidermal Sema3A and NGF levels and modulates epidermal innervation in atopic dermatitis

Tominaga

Tengara

Kamo

et al. 2009

Journal of Dermatological Science

115

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“…Psoralen acts by interfering with activator protein-1 (AP-1) in murine keratinocytes, thereby inhibiting the ability of AP-1 to bind to DNA [26]. Although the Sema3A promoter has not yet been investigated, the NGF promoter contains an AP-1 element important for transcriptional activity [27,28].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of UV-based therapy on dry skin-inducible nerve growth in acetone-treated mice

Kamo¹,

Tominaga²,

Tengara³

et al. 2011

Journal of Dermatological Science

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Inhibition of interferon-γ signaling by a mercurio-substituted dihydropsoralen in murine keratinocytes

Cited by 5 publications

References 27 publications

The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis

The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis

Psoralen-ultraviolet A therapy alters epidermal Sema3A and NGF levels and modulates epidermal innervation in atopic dermatitis

Inhibitory effects of UV-based therapy on dry skin-inducible nerve growth in acetone-treated mice

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