Hu Tairan, Lai Xiaodong, Li Li, Li Yi, Wang Meng, Zhang Haini, Yang Yan, Zhang Chong, Yan Yan, Wang Baoxi
Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cell Death Discov. 2025 Apr 12;11(1):167. doi: 10.1038/s41420-025-02471-3.
Ultraviolet B (UVB) is recognized for inducing inflammation and death of keratinocytes through the activation of death receptors and pattern recognition receptors (PRRs). Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 play pivotal roles in mediating necroptosis, which can be triggered by the activation of specific death receptors and PRRs. In this study, we observed a reduction of RIPK1 protein after UVB exposure which led to activation of Nuclear factor-kappa B (NF-κB) in HaCaT cells. This activation, in turn, promoted the production of IL-1β and TNF-α. However, RIPK1 kinase remained inactive and did not participate in cell death. Interestingly, UVB radiation triggered the activation of RIPK3 independently of RIPK1 kinase activity and subsequently induced phosphorylation of mixed-lineage kinase domain-like protein (MLKL), culminating in necroptosis and inflammation of the skin. At the same time, UVB-induced activation of RIPK3 also played a role in promoting the mitochondrial apoptotic pathway of Keratinocytes. In conclusion, UVB irradiation initiates an inflammatory response via RIPK1 pathway without necessitating its enzymatic activity. Simultaneously, RIPK3 can be activated by UVB exposure independently of RIPK1's activity, resulting in necroptosis and inflammation of the skin.
紫外线B（UVB）因通过激活死亡受体和模式识别受体（PRR）诱导角质形成细胞炎症和死亡而被人们所认识。受体相互作用蛋白激酶1（RIPK1）和RIPK3在介导坏死性凋亡中起关键作用，坏死性凋亡可由特定死亡受体和PRR的激活触发。在本研究中，我们观察到UVB照射后HaCaT细胞中RIPK1蛋白减少，这导致核因子-κB（NF-κB）激活。这种激活反过来又促进了IL-1β和TNF-α的产生。然而，RIPK1激酶仍无活性，不参与细胞死亡。有趣的是，UVB辐射独立于RIPK1激酶活性触发RIPK3激活，随后诱导混合谱系激酶样结构域蛋白（MLKL）磷酸化，最终导致皮肤坏死性凋亡和炎症。同时，UVB诱导的RIPK3激活在促进角质形成细胞的线粒体凋亡途径中也发挥了作用。总之，UVB照射通过RIPK1途径引发炎症反应，而无需其酶活性。同时，UVB照射可独立于RIPK1的活性激活RIPK3，导致皮肤坏死性凋亡和炎症。
