Down-regulation of interferon γ-activated STAT1 by UV light

Aragane, Yoshinori; Kulms, Dagmar; Luger, Thomas A.; Schwarz, Thomas

doi:10.1073/pnas.94.21.11490

Cited by 69 publications

(54 citation statements)

References 40 publications

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“…Along this line, STAT3 phosphorylation, which also appears to be involved in IL-2 signaling, was not significantly affected by UV (data not shown). In this context it is important to mention that it was previously observed that IL-6-mediated phosphorylation of STAT3 was also not inhibited by UV (15). These findings and the fact that UV is a well known activator of nuclear factor-B and AP-1 both in vitro and in vivo (39 -41) .…”

Section: Suppression Of Il-2-induced Activation Of Stat5 By Uv Is Prementioning

confidence: 76%

“…Phosphorylated STAT1 dimerizes, translocates to the nucleus where it binds to the IFN␥-activated sequences (GAS) in various promoters, and ultimately induces specific gene transcription. We observed that UV inhibits IFN␥-induced STAT1 phosphorylation and consequently STAT1 binding capacities (15). Because phosphorylation of STAT1 is a critical event in IFN␥ signaling, UV inhibits IFN␥ from exerting its biological effects via this mechanism.…”

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confidence: 74%

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Ultraviolet Radiation Inhibits Interleukin-2-induced Tyrosine Phosphorylation and the Activation of STAT5 in T Lymphocytes

Kulms¹,

Schwarz²

2001

Journal of Biological Chemistry

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UV radiation was recently found to hinder interferon-␥ from exerting its biological effects by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)-1, a crucial signal transducing protein in the interferon-␥ pathway. Because this activity by UV may contribute to its immunosuppressive properties we studied whether this is specific for STAT1 or whether UV also affects other members of the STAT family. STAT5 is crucially involved in signaling of interleukin (IL)-2, enabling up-regulation of the IL-2 receptor ␣ chain, an essential component of the high affinity IL-2 receptor. Exposure of the murine T cell line CTLL to IL-2 caused tyrosine phosphorylation of STAT5 that was remarkably reduced when cells were exposed to UV. Accordingly, STAT5 binding activity was significantly impaired in UV-exposed cells. In contrast, IL-2-induced tyrosine phosphorylation of the kinases Jak1 and Jak3 located upstream of STAT5 was not affected by UV. The effect of UV on STAT5 phosphorylation was antagonized by orthovanadate, implying involvement of a phosphatase in this process. Accordingly, up-regulation of the IL-2 receptor ␣ chain was reduced in cells that were treated with IL-2 plus UV. Because STAT5-mediated IL-2 effects are vital for normal immune functions, inhibition of STAT5 signaling by UV may contribute to its well known immunosuppressive properties.UV radiation and, in particular, UVB with a wavelength range between 290 and 320 nm, represents one of, if not the most important environmental danger to human health. Its hazardous effects include the induction of skin cancer (1), suppression of the immune system (2), and chronic skin damage e.g. premature skin aging (3). The effects of UV on the cellular level include the induction of apoptotic cell death (4), the induction of inflammatory processes via the release of inflammatory cytokines (5), and the inhibition of cellular immune responses (2). In particular, the immunosuppressive properties of UV are of major biological relevance, because suppression of the immune system by UV is not only responsible for the exacerbation of infectious diseases following UV exposure, e.g. herpes simplex (6), but also contributes to the induction of skin cancer (7). Hence, understanding of the mechanisms by which UV suppresses the immune system is of primary importance. UV suppresses the immune system in multiple ways (2). Just to name a few, it inhibits antigen presentation by down-regulating the surface expression of accessory molecules (8), it induces the generation of T suppressor cells, which inhibit antigenspecific immune responses (9), and it induces the release of immunosuppressive cytokines e.g. interleukin (IL) 1 -10, tumor necrosis factor ␣, and transforming growth factor ␤ (reviewed in Refs. 10 and 11).Recently, we obtained the first evidence that UV does not only have the ability to influence the release of cytokines but that it can also interfere with the biological activity of immunomodulatory mediators. Specifically, we demonstrated that UV...

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Section: Suppression Of Il-2-induced Activation Of Stat5 By Uv Is Prementioning

confidence: 76%

mentioning

confidence: 74%

Ultraviolet Radiation Inhibits Interleukin-2-induced Tyrosine Phosphorylation and the Activation of STAT5 in T Lymphocytes

Kulms¹,

Schwarz²

2001

Journal of Biological Chemistry

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“…We used anisomycin as stress stimulus for MEFs instead of LPS, because the expression of some essential components of the LPS signaling pathway is restricted to hematopoietic cells (26). We also ruled out UV light as inducer, because it has been shown that this stimulus down-regulates IFN-␥-induced Tyr-701 phosphorylation of STAT1 by unknown mechanisms (27).…”

Section: Ifn-␥-stimulated Expression Of the Stat1 Target Gene Irf1 Domentioning

confidence: 99%

p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation

Ramsauer

Sadzak

Porrás

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

118

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“…It interferes with Th1 type cytokine production, such as IFN-γ and IL-7, and their signaling pathways on murine keratinocytes (Aragane et al, 1997;Yoshimori et al, 1997). The immunosuppressive effect of gamma irradiation is also well known, but its mechanism has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Gamma Irradiation-reduced IFN-γ Expression, STAT1 Signals, and Cell-mediated Immunity

Han¹,

Song²,

Yun³

et al. 2002

BMB Reports

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The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon γ (IFN-γ). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-γ-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-γ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

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Down-regulation of interferon γ-activated STAT1 by UV light

Cited by 69 publications

References 40 publications

Ultraviolet Radiation Inhibits Interleukin-2-induced Tyrosine Phosphorylation and the Activation of STAT5 in T Lymphocytes

Ultraviolet Radiation Inhibits Interleukin-2-induced Tyrosine Phosphorylation and the Activation of STAT5 in T Lymphocytes

p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation

Gamma Irradiation-reduced IFN-γ Expression, STAT1 Signals, and Cell-mediated Immunity

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