Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy

Morita, Akimichi; Werfel, Thomas; Stege, Helger; Ahrens, Constanze; Karmann, Karin; Grewe, Markus; Grether‐Beck, Susanne; Ruzicka, Thomas; Kapp, Alexander; Klotz, Lars‐Oliver; Sies, Helmut; Krutmann, Jean

doi:10.1084/jem.186.10.1763

Cited by 269 publications

(190 citation statements)

References 29 publications

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“…Fas ligand is not involved in singlet oxygen-induced apoptosis of HL-60 cells Aragane et al (1998) have demonstrated that UVinduced clustering of Fas is functionally relevant for the induction of apoptosis and Morita et al (1997) have reported that singlet oxygen mediates UVAinduced Fas ligand expression in T helper cells. To determine whether singlet oxygen-induced apoptosis depends on Fas ligand in our system, cells were incubated with medium containing an anti-Fas neutralizing antibody (1 mg/ml) for 1 h. Following photosensitization, the same medium was immediately added to HL-60 cells which were incubated for 2.5 h before harvesting.…”

Section: Singlet Oxygen-induced Aggregation Of Fas and Recruitment Ofmentioning

confidence: 99%

“…ROS, including singlet oxygen, have been reported to mediate UV-induced apoptosis (Dong et al, 2000;Morita et al, 1997). To examine whether singlet oxygen was able to induce aggregation of Fas and association of FADD with Fas, we ®rst analysed the distribution of Fas in the membrane using confocal laser scanning microscopy.…”

Section: Singlet Oxygen-induced Aggregation Of Fas and Recruitment Ofmentioning

confidence: 99%

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Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation

2001

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Although activation of protein kinase C (PKC) inhibits apoptosis induced by a variety of stimuli including singlet oxygen, the step at which PKC activation interferes with apoptotic signaling is not well de®ned. We have shown previously that caspase-8 and p38 mediate singlet oxygen-induced apoptosis in HL-60 cells. In this study, we investigated the in¯uence of PKC on regulation of the caspase and p38 pathways initiated by singlet oxygen. Singlet oxygen induced Fas clustering and subsequent recruitment of FADD and caspase-8. Treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, did not a ect the binding of caspase-8 to the aggregated Fas. Surprisingly, under the same conditions PKC activation was still able to prevent singlet oxygen-induced activation of caspase-8 and block its downstream signaling events including cleavage of Bid and caspase-3, decrease in mitochondrial transmembrane potential and release of cytochrome c from mitochondria. Inhibition of PKC by GF109203 or H7 counteracted the TPA-mediated e ects on the cleavage of caspases -3 and -8. However, neither activation nor inhibition of PKC a ected p38 phosphorylation. These data indicate that PKC inhibits singlet oxygen-induced apoptosis by blocking activation of caspase-8. Oncogene (2001) 20, 6764 ± 6776.

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Section: Singlet Oxygen-induced Aggregation Of Fas and Recruitment Ofmentioning

confidence: 99%

Section: Singlet Oxygen-induced Aggregation Of Fas and Recruitment Ofmentioning

confidence: 99%

Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation

2001

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“…Other effects such as downregulated IFN-g expression in skin lesions of atopic dermatitis and a reduction of inflammatory infiltrates in the skin by UVA-1 irradiation have also been shown. [20][21][22][23] UVA-1 also caused phenotypic and functional maturation of migrating dermal DCs into potent APCs. These data underline the evidence for UVA's immunosuppressive abilities.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16] Long-wavelength UVA (340-400 nm UVA-1) phototherapy has been described as a successful treatment option for atopic dermatitis, localized scleroderma and other T-cellderived skin diseases. [17][18][19][20][21][22][23][24] Equipment capable of delivering this waveband has been available since 1981, but only over the past decade have studies assessing the therapeutic potential of UVA-1 been published. UVA-1 irradiation has many advantages over classic 8-methyoxypsoralen plus UV light therapy.…”

Section: Introductionmentioning

confidence: 99%

UVA (UVA-1) therapy for the treatment of acute GVHD of the skin

Schlaak

Schwind

Wetzig³

et al. 2010

Bone Marrow Transplant

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Long-wavelength UVA (340-400 nm UVA-1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and T-cell-derived skin diseases. We retrospectively investigated 70 patients with acute cutaneous GVHD after allogeneic haematopoietic cell transplantation or donor lymphocyte infusion. Complete and partial responses with a median duration of 10 months were achieved in 49 (70%) and 17 (24.3%) patients, respectively. Overall, 47 (67.1%) patients were not treated with systemic steroids. Furthermore, immunosuppression could be tapered in 24 (34.3%) patients while they were receiving UVA-1 treatment. Responses were seen irrespective of age or type of conditioning. Treatment was very well tolerated. After a median follow-up of 18 (range 10-60) months, three patients developed epithelial skin neoplasia. We conclude that UVA-1 therapy is feasible, well tolerated and can be an effective treatment for acute GVHD of the skin, thereby avoiding the use of systemic steroids and/or allowing a more rapid tapering of systemic immunosuppression in a substantial number of patients. The results of this retrospective analysis warrant larger, prospective studies and the effectiveness of UVA-1 therapy should be compared with other established treatment modalities.

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“…UVA1 phototherapy induces apoptosis of skin infiltrating T cells and thereby causes a gradual reduction of the inflammatory infiltrate. 24,25 In addition, in vitro experiments showed that UVA1 radiation is a potent inducer of the immunosuppressive cytokine interleukin 10 in human keratinocytes. 26 Previous reports showed a dose-dependent upregulation of collagenase activity, which could be responsible for the clinical improvement seen in patients with scleroderma.…”

Section: Uva1 Phototherapy For Gvhd Of the Skin T Wetzig Et Almentioning

confidence: 99%

Medium dose long-wavelength ultraviolet A (UVA1) phototherapy for the treatment of acute and chronic graft-versus-host disease of the skin

Wetzig

Sticherling

et al. 2005

Bone Marrow Transplant

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Summary:Long-wavelength ultraviolet A (340-400 nm UVA1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and other T-cell-derived skin diseases. UVA1 as an adjunct to systemic immunosuppressive treatment was found to be safe, and effective in 10 patients with chronic cutaneous (seven lichenoid and three sclerodermoid) graft-versus-host disease (GVHD) after stem cell transplantation. Complete and partial responses were achieved in six (60%), and in three (30%) patients, respectively. One patient had improvement of sclerotic skin lesions. At a median follow-up of 14 months, two patients with lichenoid lesions relapsed. Both responded to another treatment cycle. Furthermore, we treated seven patients with UVA1 as primary therapy for acute cutaneous GVHD grades II and III in a pilot experience. Five patients had a complete response with no relapse at a median follow-up of 9 months after UVA1. Two patients showed no response and systemic steroids had to be started. UVA1 therapy is feasible, well tolerated and can be effective in treating chronic as well as acute GVHD confined to the skin thereby avoiding systemic steroids. Our results should be confirmed in larger studies and the effectiveness of UVA1 compared to other established treatment modalities. Bone Marrow Transplantation (2005) 35, 515-519.

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Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy

Cited by 269 publications

References 29 publications

Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation

Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation

UVA (UVA-1) therapy for the treatment of acute GVHD of the skin

Medium dose long-wavelength ultraviolet A (UVA1) phototherapy for the treatment of acute and chronic graft-versus-host disease of the skin

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