Airborne particulate matter (PM10) induces cell invasion through Aryl Hydrocarbon Receptor and Activator Protein 1 (AP-1) pathway deregulation in A549 lung epithelial cells.

Background: Particulate matter with an aerodynamic size ≤ 10 μm (PM₁₀) is a risk factor for lung cancer development, mainly because some components are highly toxic. Polycyclic aromatic hydrocarbons (PAHs) are present in PM₁₀, such as benzo[a]pyrene (BaP), which is a well-known genotoxic and carcinogenic compound to humans, capable of activating AP-1 transcription factor family genes through the Aryl Hydrocarbon Receptor (AhR). Because effects of BaP include metalloprotease 9 (MMP-9) activation, cell invasion, and other pathways related to carcinogenesis, we aimed to demonstrate that PM₁₀ (10 µg/cm²) exposure induces the activation of AP-1 family members as well as cell invasion in lung epithelial cells, through AhR pathway. Methods and results: The role of the AhR gene in cells exposed to PM₁₀ (10 µg/cm²) and BaP (1µM) for 48 h was evaluated using AhR-targeted interference siRNA. Then, the AP-1 family members (c-Jun, Jun B, Jun D, Fos B, C-Fos, and Fra-1), the levels/activity of MMP-9, and cell invasion were analyzed. We found that PM₁₀ increased AhR levels and promoted its nuclear localization in A549 treated cells. Also, PM₁₀ and BaP deregulated the activity of AP-1 family members. Moreover, PM₁₀ upregulated the secretion and activity of MMP-9 through AhR, while BaP had no effect. Finally, we found that cell invasion in A549 cells exposed to PM₁₀ and BaP is modulated by AhR. Conclusion: Our results demonstrated that PM₁₀ exposure induces upregulation of the c-Jun, Jun B, and Fra-1 activity, the expression/activity of MMP-9, and the cell invasion in lung epithelial cells, effects mediated through the AhR. Also, the Fos B and C-Fos activity were downregulated. In addition, the effects induced by PM₁₀ exposure were like those induced by BaP, which highlights the potentially toxic effects of the PM₁₀ mixture in lung epithelial cells. Highlights: PM₁₀ exposure upregulated c-Jun, Jun B, and Fra-1 activity through AhR in A549 cells. PM₁₀ exposure downregulated the Fos B and C-Fos 1 activity through AhR in A549 cells. PM₁₀ exposure increases levels/activity of MMP-9, an effect mediated by AhR. PM₁₀ exposure induced cell invasion in A549 cells, an effect mediated by AhR. PM₁₀ exposure induces similar effects to BaP in A549 cells, through AhR pathway. [ABSTRACT FROM AUTHOR]