Tacrolimus may play a role in dermatitis and radiation-induced skin injury through cellular senescence

Abstract

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects, resulting in radiation-induced skin injury (RSI). Premature cellular senescence, caused by oxidative stress and/or DNA damage from chemical or physical agents, leads to the decrease of cellular proliferation and physiological function. Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury. Atopic dermatitis and RSI have similar inflammatory symptoms. The treatment of tacrolimus (TAC) in atopic dermatitis may be associated with premature cellular senescence. TAC can prevent the onset of cellular senescence by inactivating the p38 mitogen-activated protein kinase (p38 ​MAPK). The activation of p38 ​MAPK can induce the senescence-associated secretory phenotype (SASP) by enhancing the transcriptional activity of nuclear factor kappa-B (NF-κB), which ultimately leads to premature cellular senescence. FK506 binding protein 51 (FKBP51) exhibits resistance to ionizing radiation, but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study. This review discusses the mechanism of cellular senescence in RSI and the role of TAC in both dermatitis and RSI.

Keywords

• Tacrolimus
• Premature cellular senescence
• Radiation-induced skin injury
• p38 ​MAPK
• NF-κB