Background: Sphingosine kinase 1 (SPHK1) and heat shock protein 27 (HSP27) are important for antioxidant and anti-inflammatory effects after red light irradiation in an inflammatory model. Objective: The purpose of the present study was to evaluate whether SPHK1 and HSP27 work independently or are dependent on some other regulator after 625 nm light-emitting diode irradiation in the human keratinocyte (HaCaT) cell line. Methods: Differentially expressed genes (DEGs) were identified between groups with or without 625 nm photobiomodulation (PBM) in the inflammatory model. Potential transcription factors (TFs) of key DEGs were predicted using the iRegulon plugin. The mechanism was investigated by analyzing mRNA and protein expression levels, prostaglandin E2 levels, and intracellular reactive oxygen species (ROS) in phorbol 12-myristate 13-acetate (PMA)-induced HaCaT cells after 625 nm PBM. Results: A total of 6 TFs (e.g., E2F1) and 51 key DEGs (e.g., SPHK1) were identified after 625 nm PBM in PMA-stimulated HaCaT cells. E2F1 worked as a regulator of SPHK1; however, it did not affect HSP27. E2F1 knockdown drastically decreased the SPHK1 expression level and increased the intracellular ROS, as well as the expression levels of inflammation-related proteins in PMA-induced HaCaT cells. In addition, the inhibition of HSP27 decreased the anti-inflammatory effect of 625 nm PBM. Conclusions: E2F1 worked as a TF of SPHK1 and exhibited anti-inflammatory and antioxidative effects through SPHK1 in PMA-induced HaCaT cells after 625 nm PBM. HSP27 is essential for the 625 nm PBM-induced anti-inflammatory function. Therefore, E2F1/SPHK1 and HSP27 could be used as potential biomarkers for anti-inflammatory therapy with 625 nm PBM.
Keywords: 625 nm; anti-inflammation; anti-oxidant; light-emitting diode irradiation; transcription factor.