Modulation of Autophagy on Cinnamaldehyde Induced THP-1 Cell Activation

Cinnamaldehyde (CIN), which is a cosmetic fragrance allergen regulated by the European Union, can induce allergic contact dermatitis in consumers, reducing their quality of life. Autophagy may be associated with the dendritic cell (DC) response to chemical sensitizers. We hypothesized that CIN would activate DCs through autophagy during skin sensitization. In this study, Tohoku Hospital Pediatrics-1 cells (THP-1 cells) were used as an in vitro DC model, and we evaluated the expression of cell activation markers, intracellular oxidative stress, and autophagy pathway-related genes in response to CIN in THP-1 cells. CIN exposure activated THP-1 cells, which presented increases in CD54 and CD86 expression and ROS generation. Transcriptomic analysis revealed that the genes that were differentially expressed after CIN stimulation were mostly associated with autophagy. The autophagy markers LC3B, p62, and ATG5 had upregulated mRNA and protein levels after CIN exposure. Furthermore, the effects of the autophagy inhibitor Baf-A1 and the autophagy activator rapamycin were investigated on CIN-treated cells. Pretreatment with Baf-A1 in THP-1 cells impaired autophagic flux and dramatically promoted cell activation and oxidative stress triggered by CIN. Conversely, rapamycin inhibited cell activation and the ROS content in CIN-challenged cells while increasing autophagy levels via a reduction in mTOR expression. These results suggest that the autophagy pathway has a pivotal influence on the regulation of CIN-induced activation in THP-1 cells, which provides new insight into the pathogenesis and precise therapeutic strategies for ACD.