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

• Published in: Molecular biology reports Vol. 50; no. 1; pp. 107 - 119
• Main Authors: Morales-Bárcenas, Rocío, Sánchez-Pérez, Yesennia, Santibáñez-Andrade, Miguel, Chirino, Yolanda I., Soto-Reyes, Ernesto, García-Cuellar, Claudia M.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 2023; Springer Nature B.V
• Subjects: A549 Cells; Activator protein 1; AhR gene; Airborne particulates; Animal Anatomy; Animal Biochemistry; Benzo(a)pyrene; Biomedical and Life Sciences; c-Fos protein; c-Jun protein; Carcinogenesis; Cell activation; Epithelial cells; Epithelial Cells - metabolism; Fra1 protein; Gelatinase B; Genotoxicity; Histology; Humans; Hydrocarbons; Life Sciences; Localization; Lung - metabolism; Lung cancer; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Metalloproteinase; Morphology; Original Article; Particulate matter; Particulate Matter - toxicity; Polycyclic aromatic hydrocarbons; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Risk factors; siRNA; Transcription Factor AP-1 - genetics; Transcription factors; Activator protein 1 (AP-1); Aryl hydrocarbon receptor (AhR); Cellular invasion; PM; MMP-9; PM10
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07986-x

Background Particulate matter with an aerodynamic size ≤ 10 μm (PM 10 ) is a risk factor for lung cancer development, mainly because some components are highly toxic. Polycyclic aromatic hydrocarbons (PAHs) are present in PM 10 , 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 PM 10 (10 µg/cm 2 ) 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 PM 10 (10 µg/cm 2 ) 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 PM 10 increased AhR levels and promoted its nuclear localization in A549 treated cells. Also, PM 10 and BaP deregulated the activity of AP-1 family members. Moreover, PM 10 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 PM 10 and BaP is modulated by AhR. Conclusion Our results demonstrated that PM 10 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 PM 10 exposure were like those induced by BaP, which highlights the potentially toxic effects of the PM 10 mixture in lung epithelial cells. Highlights PM 10 exposure upregulated c-Jun, Jun B, and Fra-1 activity through AhR in A549 cells. PM 10 exposure downregulated the Fos B and C-Fos 1 activity through AhR in A549 cells. PM 10 exposure increases levels/activity of MMP-9, an effect mediated by AhR. PM 10 exposure induced cell invasion in A549 cells, an effect mediated by AhR. PM 10 exposure induces similar effects to BaP in A549 cells, through AhR pathway.