Expression of the Platelet-activating Factor Receptor Results in Enhanced Ultraviolet B Radiation-induced Apoptosis in a Human Epidermal Cell Line

Barber, Lisa A.; Spandau, Dan F.; Rathman, Sara C.; Murphy, Robert C.; Johnson, Christopher; Kelley, Susan W.; Hurwitz, Steven A.; Travers, Jeffrey B.

doi:10.1074/jbc.273.30.18891

Cited by 76 publications

(76 citation statements)

References 46 publications

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“…A number of other soluble factors are released within the skin after exposure to inflammatory doses of UV, including cis-urocanic acid (cis-UCA) 52 and the oxidized membrane lipid PAF. 53 To determine whether cis-UCA ( Figure 6F) or PAF ( Figure 6G) could directly induce IL-33 expression in fibroblasts, we incubated MEFs with each of these factors for 1 hour or 4 hours. As can be seen in Figure 6, E-H, only PAF significantly upregulated IL-33 expression in these cells.…”

Section: Uvb and Paf Induce Il-33 Expression In Skinmentioning

confidence: 99%

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Byrne

Beaugie

O’Sullivan

et al. 2011

The American Journal of Pathology

105

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The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skininfiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

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Section: Uvb and Paf Induce Il-33 Expression In Skinmentioning

confidence: 99%

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Byrne

Beaugie

O’Sullivan

et al. 2011

The American Journal of Pathology

105

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“…Expression of the PAF-receptor in the PAF-receptor-negative epithelial cell line KB results in an augmentation of UVB-mediated cytokine production and cytotoxicity 11,27 . UVB is immunosuppressive and facilitates progression of non-melanoma skin cancer, and it has been proposed 24 that PAF and/or PAF-like lipids mediate this systemic immune suppression via PAF-receptor-mediated IL-10 production.…”

Section: Paf System and Uvrmentioning

confidence: 99%

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

Konger

Marathe

Yao

et al. 2008

Prostaglandins & Other Lipid Mediators

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Ultraviolet light radiation (UVR) has profound effects upon human skin. Yet, the exact targets for UVR are unclear. Inasmuch as UVR is a known pro-oxidative stressor, one potential target for UVR could be oxidatively modified glycerophosphocholines (GPC). Importantly, recent studies demonstrate that these oxidized GPCs (ox-GPC) are potent agonists for the platelet-activating factor receptor and peroxisome proliferator-activated receptor gamma. This review discusses these new biologically active lipids and their down-stream receptor targets that provide a unique system of biosensors for detecting and responding to UVR photo-oxidation.

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“…UVB Irradiation-Epidermal cells were irradiated as described previously (12). For studies examining PAF-R agonistic activity, 10-cm dishes containing KBM cells (Ͼ90% confluent) were washed three times with HBSS, and 1 ml of prewarmed (37°C) HBSS with 0.25% bovine serum albumin was added and then UVB-irradiated (FS20 Westinghouse Electric Corp., Pittsburgh, PA).…”

Section: Methodsmentioning

confidence: 99%

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

Dy¹,

Pei²,

Travers³

1999

Journal of Biological Chemistry

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Ultraviolet B radiation (UVB) has been shown to damage human keratinocytes in part by inducing oxidative stress and cytokine production. Indeed, UVB-induced production of the pro-inflammatory and cytotoxic cytokine tumor necrosis factor ␣ (TNF-␣) has been implicated in the epidermal damage seen in response to acute solar radiation. Though the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and keratinocytes express PAF receptors linked to cytokine biosynthesis, it is not known whether PAF is involved in UVB-induced epidermal cell cytokine production. These studies examined the role of the PAF system in UVB-induced epidermal cell TNF-␣ biosynthesis using a novel model system created by retroviralmediated transduction of the PAF receptor-negative human epidermal cell line KB with the human PAF receptor (PAF-R). Treatment of PAF-R-expressing KB cells with the metabolically stable PAF-R agonist carbamoyl-PAF resulted in increased TNF-␣ mRNA and protein, indicating that activation of the epidermal PAF-R was linked to TNF-␣ production. UVB irradiation of PAF-R-expressing KB cells resulted in significant increases in both TNF-␣ mRNA and protein in comparison to UVB-treated control KB cells. However, UVB treatment up-regulated cyclooxygenase-2 mRNA levels to the same extent in both PAF-R-expressing and control KB cells. Pretreatment with the antioxidant vitamin E or the PAF-R antagonists WEB 2086 and A-85783 inhibited UVB-induced TNF-␣ production in the PAF-R-positive but not control KB cells. These studies suggest that the epidermal PAF-R may be a pharmacological target for UVB in skin.

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Expression of the Platelet-activating Factor Receptor Results in Enhanced Ultraviolet B Radiation-induced Apoptosis in a Human Epidermal Cell Line

Cited by 76 publications

References 46 publications

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

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