Ultraviolet B radiation activates NF‐κB and induces iNOS expression in HR‐1 hairless mouse skin: Role of IκB kinase‐β

Chang, Eun-Jin; Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young‐Joon

doi:10.1002/mc.20646

Cited by 24 publications

(15 citation statements)

References 55 publications

(78 reference statements)

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“…We found upregulation of iNOS expression at 4 h following UVA and UVB treatment. This corresponds with the results by Chang et al who found significantly increased iNOS level in mouse skin 6 h after UVB (0.5 J/cm 2 ) irradiation 33 . Repeated UVB exposure (80% of UVB, 7x180 mJ/cm 2 ) of SKH-1 mice induced iNOS protein increase 24 h after the last treatment 34 .…”

Section: Discussionsupporting

confidence: 92%

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Vostalová¹,

Svobodová²,

Galandáková³

et al. 2013

BIOMED PAP

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Background. Solar light generates inflammatory responses in exposed skin. These effects are generally attributed to UVB light. However, skin is exposed to a huge quantum of UVA photons as UVA is a predominant part of sunlight and the radiation used in tanning beds. We examined the effects of a single exposure to UVA and UVB wavebands on cytokine levels in skin and plasma, myeloperoxidase (MPO) activity, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in skin. Methods. Hairless mice were irradiated with either UVA (10 or 20 J/cm 2 ) or UVB (200 or 800 mJ/cm 2 ). The effects were assessed after 4/24 h. Plasma cytokine levels were evaluated using a Bio-Plex cytokine assay. Cytokine, iNOS and COX-2 levels in skin were determined by Western blot. Skin MPO activity was monitored spectrophotometrically. Results. UVB induced up-regulation of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and decrease in interleukin-10 (IL-10) mainly after 4 h. In contrast, UVA caused increase in levels of tumor necrosis factor-alpha (TNF-α) and IL-6 after 4 h and up-regulated IL-10 and interleukin-12 (IL-12) after 24 h. The increase in MPO activity from infiltrated leucocytes was observed only in UVB irradiated animals. iNOS was up-regulated 4 h after UVA and UVB treatment. No significant effect on COX-2 expression was detected. Conclusions. UVA and UVB light affected several inflammatory markers. For individual waveband, changes in plasma parameters did not correlate with those in skin. Thus evaluation of plasma samples cannot simply be replaced by determination in skin specimens and vice versa.

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Section: Discussionsupporting

confidence: 92%

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Vostalová¹,

Svobodová²,

Galandáková³

et al. 2013

BIOMED PAP

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“…Moreover, the transcriptional activation of NOX-4 is regulated in part by NF-κB in TNFα-stimulated human aortic smooth muscle cells [22]. We have previously reported that UVB radiation activates NF-κB in hairless mouse skin at 1 h which persists until 6 h post-irradiation [19]. Since NF-κB is involved in the transcriptional activation of COX-2 [27] and NOX-4 [22], we examined the effect of DHA on NF-κB activation in UVB-irradiated hairless mouse skin.…”

Section: Resultsmentioning

confidence: 96%

“…Exposure to UVB radiation leads to the phosphorylation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) [19] and p38 MAP kinase [15], [17], which activates NF-κB and induces COX-2 expression [20]. The activation of p38 MAP kinase and NF-κB is also involved in the induction of NOX-4 expression in γ-radiation-stimulated lung fibroblasts [21] and tumor necrosis factor-α (TNFα)-treated human aortic smooth muscle cells [22], respectively.…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid Inhibits UVB-Induced Activation of NF-κB and Expression of COX-2 and NOX-4 in HR-1 Hairless Mouse Skin by Blocking MSK1 Signaling

et al. 2011

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Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Docosahexaenoic acid (DHA), a representative ω-3 polyunsaturated fatty acid, has been reported to possess anti-inflammatory and chemopreventive properties. In the present study, we investigated the molecular mechanisms underlying the inhibitory effects of DHA on UVB-induced inflammation in mouse skin. Our study revealed that topical application of DHA prior to UVB irradiation attenuated the expression of cyclooxygenase-2 (COX-2) and NAD(P)H:oxidase-4 (NOX-4) in hairless mouse skin. DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB (NF-κB) through the inhibition of phosphorylation of IκB kinase-α/β, phosphorylation and degradation of IκBα and nuclear translocation of p50 and p65. In addition, UVB-induced phosphorylation of p65 at the serine 276 residue was significantly inhibited by topical application of DHA. Irradiation with UVB induced phosphorylation of mitogen and stress-activated kinase-1 (MSK1), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase, and all these events were attenuated by pretreatment with DHA. Blocking ERK and p38 MAP kinase signaling by U0126 and SB203580, respectively, diminished MSK1 phosphorylation in UVB-irradiated mouse skin. Pretreatment with H-89, a pharmacological inhibitor of MSK1, abrogated UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 in mouse skin. In conclusion, topically applied DHA inhibits the UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 by blocking the phosphorylation of MSK1, a kinase downstream of ERK and p38 MAP kinase, in hairless mouse skin.

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“…Solar radiation leads to activation of NFκB in humans [58] and mice [59], although UVB-induced upstream activation of NFκB signaling molecules including IκB and IKK is inconsistent in the literature [60,61,62,63]. UVB also induces expression of TNFα [64,65], although the mechanism of UVB modulation of the TNFα promoter is poorly understood [66,67].…”

Section: Discussionmentioning

confidence: 99%

The TGFβ1 pathway is required for NFκB dependent gene expression in mouse keratinocytes

et al. 2013

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The transforming growth factor beta1 (TGFβ1) and NFκB pathways are important regulators of epidermal homeostasis, inflammatory responses and carcinogenesis. Previous studies have shown extensive crosstalk between these pathways that is cell type and context dependent, but this has not been well-characterized in epidermal keratinocytes. Here we show that in primary mouse keratinocytes, TGFβ1 induces NFκB-luciferase reporter activity that is dependent on both NFκB and Smad3. TGFβ1-induced NFκB-luciferase activity was blocked by the IκB inhibitor parthenolide, the IκB super-repressor, a dominant negative TGFβ1-activated kinase 1 (TAK1) and genetic deletion of NFκB1. Coexpression of NFκB p50 or p65 subunits enhanced NFκB-luciferase activity. Similarly, inhibition of the TGFβ1 type I receptor with SB431542 or genetic deletion of Smad3 blocked TGFβ1 induction of NFκB-luciferase. TGFβ1 rapidly induced IKK phosphorylation but did not cause a detectable decrease in cytoplasmic IκB levels or nuclear translocation of NFκB subunits, although EMSA showed rapid NFκB nuclear binding activity that could be blocked by SB431542 treatment. TNFα, a well characterized NFκB target gene was also induced by TGFβ1 and this was blocked in NFκB+/− and −/− keratinocytes and by the IκB super-repressor. To test the effects of the TGFβ1 pathway on a biologically relevant activator of NFκB, we exposed mice and primary keratinocytes in culture to UVB irradiation. In primary keratinocytes UVB caused a detectable increase in levels of Smad2 phosphorylation that was dependent on ALK5, but no significant increase in SBE-dependent gene expression. Inhibition of TGFβ1 signaling in primary keratinocytes with SB431542 or genetic deletion of Tgfb1 or Smad3 suppressed UVB induction of TNFα message. Similarly, UVB induction of TNFα mRNA was blocked in skin of Tgfb1+/− mice. These studies demonstrate that intact TGFβ1 signaling is required for NFκB-dependent gene expression in mouse keratinocytes and skin and suggest that a convergence of these pathways in the nucleus rather than the cytoplasm may be critical for regulation of inflammatory pathways in skin by TGFβ1.

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Ultraviolet B radiation activates NF‐κB and induces iNOS expression in HR‐1 hairless mouse skin: Role of IκB kinase‐β

Cited by 24 publications

References 55 publications

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Docosahexaenoic Acid Inhibits UVB-Induced Activation of NF-κB and Expression of COX-2 and NOX-4 in HR-1 Hairless Mouse Skin by Blocking MSK1 Signaling

The TGFβ1 pathway is required for NFκB dependent gene expression in mouse keratinocytes

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