期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 195, 期 2, 页码 171-179出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20011450
关键词
inflammation; lipid mediators; delayed-type hypersensitivity; tolerance/suppression; immunomodulators
资金
- NCI NIH HHS [CA 16672, T32 CA009598, R01CA 088943, R01 CA088943, R01CA 75575, T32-CA-09598-10, R01 CA075575, P30 CA016672] Funding Source: Medline
Ultraviolet (UV) radiation plays a critical role in the induction of nonmelanoma skin cancer. UV radiation is also immune suppressive, and the immune suppression induced by UV irradiation has been identified as a major risk factor for skin cancer induction. Previously, we showed that UV exposure activates a cytokine cascade involving prostaglandin (PG)E-2, interleukin (IL)-4, and IL-10 that induces immune suppression. However, the earliest molecular events that occur immediately after UV exposure, especially those upstream of PGE(2), are not well defined. UV-irradiated keratinocytes secrete the inflammatory phospholipid mediator, platelet-activating factor (PAF). Because PAF upregulates the production of immunomodulatory compounds, including PGE(2), we tested the hypothesis that UV-induced PAF activates cytokine production and initiates UV-induced immune suppression. Both UV and PAF activated cyclooxygenase (COX)-2 and IL-10 reporter gene construct transcription. PAF mimicked the effects of UV in vivo and suppressed delayed-type hypersensitivity (DTH). Furthermore, immune suppression was blocked when UV-irradiated mice were injected with PAF receptor antagonists. In addition to the well-known role of PAF as a proinflammatory lipid mediator, we propose that the PAF receptor senses cellular damage through the recognition of PAF and/ or PAF-like molecules, such as oxidized phosphatidylcholine, which activates cytokine transcription and induces systemic immune suppression.
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