Effects of Combination of 1,25(OH) 2D 3 and TLR-4 Inhibitor on the Damage to HaCaT Cells Caused by UVB Irradiation

Biomed Environ Sci. 2022 Nov 20;35(11):1051-1062. doi: 10.3967/bes2022.133.

Abstract

Objective: Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) 2D 3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) 2D 3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation.

Methods: In vitro, HaCaT cells were treated with 1,25(OH) 2D 3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm 2, then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined.

Results: Compared with the HaCaT cells treated with 1,25(OH) 2D 3 or TAK-242, the cells treated with both 1,25(OH) 2D 3 and TAK-242 showed, 1) significantly lower production of ROS ( P < 0.05); 2) significantly less apoptosis of HaCaT cells ( P < 0.05); 3) significantly lower expression of NF- κB, Caspase-8, Cyto-C, Caspase-3 ( P < 0.05).

Conclusion: The combination of 1,25(OH) 2D 3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) 2D 3 or TAK-242 alone.

Keywords: 1,25(OH)2D3; Combined effects; HaCaT cell; Toll-like receptor 4; UVB.

MeSH terms

  • Cholecalciferol / analogs & derivatives
  • HaCaT Cells*
  • Humans
  • NF-kappa B
  • Reactive Oxygen Species
  • Toll-Like Receptor 4*
  • Ultraviolet Rays / adverse effects

Substances

  • ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
  • NF-kappa B
  • Reactive Oxygen Species
  • Toll-Like Receptor 4
  • Cholecalciferol