Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response.
Anastasija MaleševićDina TucovićJelena KulašIvana MirkovDušanka PopovićMaja Čakić MiloševićAleksandra Popov AleksandrovPublished in: International journal of molecular sciences (2024)
The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.
Keyphrases
- induced apoptosis
- wound healing
- lymph node
- cell cycle arrest
- gene expression
- soft tissue
- immune response
- endoplasmic reticulum stress
- cell death
- single cell
- dendritic cells
- rheumatoid arthritis
- radiation therapy
- neoadjuvant chemotherapy
- toll like receptor
- dna damage
- binding protein
- sentinel lymph node
- pi k akt
- heat stress