Biomol Ther.  2019 Nov;27(6):570-576. 10.4062/biomolther.2019.025.

Particulate Matter-Induced Aryl Hydrocarbon Receptor Regulates Autophagy in Keratinocytes

• Jang HS
• Lee JE
• Myung CH
• Park JI
• Jo CS
• Hwang JS

• KMID: 2462884
• DOI: http://doi.org/10.4062/biomolther.2019.025

Abstract

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.

Keyword

PM; AhR; Autophagy; LC3; p62; Keratinocytes

MeSH Terms

Autophagy*
Cytochrome P-450 CYP1A1
Epidermis
Keratinocytes*
Negotiating
Organelles
Particulate Matter
Receptors, Aryl Hydrocarbon*
RNA, Small Interfering
Cytochrome P-450 CYP1A1
Particulate Matter
RNA, Small Interfering
Receptors, Aryl Hydrocarbon