Solar UVB light causes damage to the outermost layer of skin. This insult induces rapid local responses, such as dermal inflammation, keratinocyte cell death, and epidermal thickening, all of which have traditionally been associated with DNA damage response signaling. Another stress response that is activated by UVB light is the ribotoxic stress response (RSR), which depends on the ribosome-associated mitogen-activated protein 3 kinases (MAP3K) ZAKα and culminates in p38 and JNK activation. Using ZAK knockout mice, we here show that it is the RSR that is responsible for the early manifestation of UVB-induced skin inflammation and keratinocyte death and subsequent proliferation in vivo. We also show that the RSR controls both p38-mediated pyroptotic and JNK-mediated apoptotic programmed cell death of human keratinocytes in vitro. In sum, our work highlights that skin cells rely on a cytoplasmic and ribosomal stress signal rather than a nuclear and DNA-templated signal for rapid inflammatory responses to UV exposure.

中文翻译：

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核糖毒性应激反应在体内紫外线照射的皮肤中驱动急性炎症、细胞死亡和表皮增厚


太阳 UVB 光会对皮肤的最外层造成伤害。这种损伤会诱导快速的局部反应，例如皮肤炎症、角质形成细胞死亡和表皮增厚，所有这些传统上都与 DNA 损伤反应信号有关。另一种被 UVB 光激活的应激反应是核糖毒性应激反应 （RSR），它依赖于核糖体相关的丝裂原活化蛋白 3 激酶 （MAP3K） ZAKα，并最终导致 p38 和 JNK 激活。使用 ZAK 敲除小鼠，我们在这里表明，RSR 负责 UVB 诱导的皮肤炎症和角质形成细胞死亡以及随后的 体内增殖的早期表现。我们还表明，RSR 在 体外控制 p38 介导的焦亡和 JNK 介导的人类角质形成细胞凋亡程序性细胞死亡。总之，我们的工作强调，皮肤细胞依赖于细胞质和核糖体应激信号，而不是核和 DNA 模板信号来对紫外线照射做出快速炎症反应。