title: Ultraviolet radiation damages self noncoding RNA and is detected by TLR3.
abstract: Exposure to ultraviolet B (UVB) radiation from the sun can result in sunburn, premature aging and carcinogenesis, but the mechanism responsible for acute inflammation of the skin is not well understood. Here we show that RNA is released from keratinocytes after UVB exposure and that this stimulates production of the inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) from nonirradiated keratinocytes and peripheral blood mononuclear cells (PBMCs). Whole-transcriptome sequencing revealed that UVB irradiation of keratinocytes induced alterations in the double-stranded domains of some noncoding RNAs. We found that this UVB-damaged RNA was sufficient to induce cytokine production from nonirradiated cells, as UVB irradiation of a purified noncoding RNA (U1 RNA) reproduced the same response as the one we observed to UVB-damaged keratinocytes. The responses to both UVB-damaged self-RNAs and UVB-damaged keratinocytes were dependent on Toll-like receptor 3 (TLR3) and Toll-like receptor adaptor molecule 1 (TRIF). In response to UVB exposure, Tlr3(-/-) mice did not upregulate TNF-α in the skin. Moreover, TLR3 was also necessary for UVB-radiation-induced immune suppression. These findings establish that UVB damage is detected by TLR3 and that self-RNA is a damage-associated molecular pattern that serves as an endogenous signal of solar injury.
authors: Division of Dermatology, University of California, San Diego, San Diego, California, USA; Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
authors: Jamie J
authors: JJ
authors: Bernard
authors: Christopher
authors: C
authors: Cowing-Zitron
authors: Teruaki
authors: T
authors: Nakatsuji
authors: Beda
authors: B
authors: Muehleisen
authors: Jun
authors: J
authors: Muto
authors: Andrew W
authors: AW
authors: Borkowski
authors: Laisel
authors: L
authors: Martinez
authors: Eric L
authors: EL
authors: Greidinger
authors: Benjamin D
authors: BD
authors: Yu
authors: Richard L
authors: RL
authors: Gallo
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000502:physiology; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D007962:Leukocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012330:RNA, Double-Stranded / Q000235:genetics / Q000528:radiation effects*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012342:RNA, Small Nuclear / Q000235:genetics / Q000528:radiation effects*; D012867:Skin / Q000528:radiation effects*; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015850:Interleukin-6; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D012342:RNA, Small Nuclear; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; C508600:IL6 protein, human; C476286:Ticam1 protein, mouse; C495344:TLR3 protein, human; C519703:TLR3 protein, mouse; C405483:U1 small nuclear RNA; C577686:interleukin-6, mouse