Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with α-naphthoflavone (α-NF), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with α-NF or used an siRNA against AhR. Expression of LC3-ІІ induced by PM was decreased in a dose dependent manner by α-NF. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-ІІ and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.

1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) is a well-characterized dopamine β-hydroxylase inhibitor that prevents 6-hydroxydopamine-induced degenerative neuronal disease. However, the effect of PTTU on melanogenesis has not been reported. In this study, we examined the effect of PTTU on melanogenesis and studied its mechanism of action. We found that PTTU decreased melanin biosynthesis in a dose-dependent manner in normal human epidermal melanocytes (NHEMs). PTTU also inhibited tyrosinase catalytic activity in NHEMs. Moreover, PTTU treatment led to reduced protein levels of tyrosinase in NHEMs, while the protein levels of tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor were not affected. However, PTTU treatment did not affect the mRNA expression of tyrosinase. We found that PTTU-accelerated tyrosinase degradation via the ubiquitin-dependent proteasome pathway. In summary, we found that PTTU decreased melanin biosynthesis by decreasing the enzymatic activity and stability of tyrosinase. Our results indicate that PTTU could be used as a depigmentation agent for hyperpigmentation disorder.