Ultraviolet radiation damages self noncoding RNA and is detected by TLR3

Jamie J. Bernard, Christopher Cowing-Zitron, Teruaki Nakatsuji, Beda Muehleisen, Jun Muto, Andrew W. Borkowski, Laisel Martinez, Eric L Greidinger, Benjamin D. Yu, Richard L. Gallo

Research output: Contribution to journalArticle

213 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1286-1290
Number of pages5
JournalNature Medicine
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2012

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Toll-Like Receptor 3
Untranslated RNA
Radiation damage
Keratinocytes
Ultraviolet radiation
Radiation
RNA
Skin
Tumor Necrosis Factor-alpha
Irradiation
Cytokines
Sunburn
Premature Aging
Toll-Like Receptors
Solar System
Transcriptome
Sun
Interleukin-6
Blood Cells
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bernard, J. J., Cowing-Zitron, C., Nakatsuji, T., Muehleisen, B., Muto, J., Borkowski, A. W., ... Gallo, R. L. (2012). Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nature Medicine, 18(8), 1286-1290. https://doi.org/10.1038/nm.2861

Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. / Bernard, Jamie J.; Cowing-Zitron, Christopher; Nakatsuji, Teruaki; Muehleisen, Beda; Muto, Jun; Borkowski, Andrew W.; Martinez, Laisel; Greidinger, Eric L; Yu, Benjamin D.; Gallo, Richard L.

In: Nature Medicine, Vol. 18, No. 8, 01.08.2012, p. 1286-1290.

Research output: Contribution to journalArticle

Bernard, JJ, Cowing-Zitron, C, Nakatsuji, T, Muehleisen, B, Muto, J, Borkowski, AW, Martinez, L, Greidinger, EL, Yu, BD & Gallo, RL 2012, 'Ultraviolet radiation damages self noncoding RNA and is detected by TLR3', Nature Medicine, vol. 18, no. 8, pp. 1286-1290. https://doi.org/10.1038/nm.2861
Bernard JJ, Cowing-Zitron C, Nakatsuji T, Muehleisen B, Muto J, Borkowski AW et al. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nature Medicine. 2012 Aug 1;18(8):1286-1290. https://doi.org/10.1038/nm.2861
Bernard, Jamie J. ; Cowing-Zitron, Christopher ; Nakatsuji, Teruaki ; Muehleisen, Beda ; Muto, Jun ; Borkowski, Andrew W. ; Martinez, Laisel ; Greidinger, Eric L ; Yu, Benjamin D. ; Gallo, Richard L. / Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. In: Nature Medicine. 2012 ; Vol. 18, No. 8. pp. 1286-1290.
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