Heavy ion radiation induces pyroptosis in skin keratinocytes through a mitogen-activated protein kinase signaling pathway.

Purpose: To elucidate the mechanisms underlying pyroptosis in skin due to heavy ion radiation.

Materials and methods: Human keratinocytes (HaCaT cells) were irradiated with different doses of X-rays and ¹²C ions. Clonogenic survival, CCK-8 cell proliferation, and micronucleus assays were performed to assess the radiosensitivity of HaCaT cells. The pyroptosis-related, inflammation-related, and MAPK/NF-κB signaling pathway proteins were detected by Western-blotting.

Results: ¹²C ion radiation caused more severe damage to HaCaT cells than X-rays. The former induced pyroptosis in the HaCaT cells in a dose-dependent manner. Heavy ion-induced pyroptosis was activated by the Caspase-4/Caspase-5/Gasdermin D (GSDMD) pathway, which was regulated by the MAPK/NF-κB signaling pathway.

Conclusions: ¹²C ion irradiation induced pyroptosis in human keratinocytes by a non-classical pathway via the activation of MAPK/NF-κB signaling pathway. The findings may be used to guide further research on targeted interventions to reduce skin damage and optimize treatment strategies in the future.