Effects of natural killer cell‑conditioned medium on UVB‑induced photoaging in human keratinocytes and a human reconstructed skin model.

Natural killer (NK) cells produce various cytokines, including interleukin (IL)‑1β, IL‑6, IL‑10, IL‑12, interferon γ, tumor necrosis factor α and transforming growth factor β, which are critical in modulating immune responses. NK cell‑conditioned medium (NK‑CdM), rich in cytokines, has potential applications in therapy and healing. The present study aimed to investigate the protective effect of NK‑CdM against ultraviolet B (UVB)‑mediated photoaging using in vitro and ex vivo models. In human keratinocyte cell line (HaCaT cells), NK‑CdM mitigated UVB‑induced cytotoxicity and suppressed the production of reactive oxygen species. NK‑CdM enhanced the mRNA expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) and inhibited the reduction in SOD1 and CAT expression levels caused by UVB irradiation. Furthermore, NK‑CdM inhibited the UVB‑mediated nuclear translocation of nuclear factor erythroid 2‑related factor 2. NK‑CdM also prevented UVB‑induced downregulation of filaggrin and involucrin and attenuated the UVB‑induced reduction in hyaluronan synthase (HAS)1, HAS2, HAS3, aquaporin‑3 and hyaluronan levels. Notably, NK‑CdM upregulated the expression of elongation of very long chain fatty acids (ELOVL) enzymes, including ELOVL1, ELOVL5 and ELOVL6, as well as ceramide synthases (CerS), specifically CerS2 and CerS3. Furthermore, NK‑CdM inhibited the UVB‑induced reduction in the levels of these proteins. Overall, these findings suggested that NK‑CdM has the potential to prevent UVB‑mediated photoaging and promote skin health.