Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment

Lam, Rachel; Haider, Syed H.; Crowley, George; Caraher, Erin J.; Ostrofsky, Dean F.; Talusan, Angela; Kwon, Sophia; Prezant, David J.; Wang, Yuyan; Liu, Mengling; Nolan, Anna

doi:10.3390/ijerph17124318

Open AccessArticle

Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment

by

Rachel Lam

^1,†

,

Syed H. Haider

^1,†,

George Crowley

¹,

Erin J. Caraher

¹,

Dean F. Ostrofsky

¹,

Angela Talusan

¹

,

Sophia Kwon

¹

,

David J. Prezant

^2,3,

Yuyan Wang

⁴,

Mengling Liu

^4,5

and

Anna Nolan

^1,2,5,*

¹

Division of Pulmonary, Department of Medicine, Critical Care and Sleep Medicine, New York University (NYU) School of Medicine, New York, NY 10016, USA

²

Bureau of Health Services and Office of Medical Affairs, Fire Department of New York, Brooklyn, NY 11201, USA

³

Pulmonary Medicine Division, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY 10461, USA

⁴

Division of Biostatistics, Departments of Population Health, New York University School of Medicine, New York, NY 10016, USA

⁵

Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA

^*

Author to whom correspondence should be addressed.

^†

Denotes equivalent contribution.

Int. J. Environ. Res. Public Health 2020, 17(12), 4318; https://doi.org/10.3390/ijerph17124318

Submission received: 23 April 2020 / Revised: 10 June 2020 / Accepted: 11 June 2020 / Published: 17 June 2020

(This article belongs to the Special Issue Environmental Pollution and Oxidative Status)

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Abstract

World Trade Center particulate matter (WTC-PM)-exposed firefighters with metabolic syndrome (MetSyn) have a higher risk of WTC lung injury (WTC-LI). Since macrophages are crucial innate pulmonary mediators, we investigated WTC-PM/lysophosphatidic acid (LPA) co-exposure in macrophages. LPA, a low-density lipoprotein metabolite, is a ligand of the advanced glycation end-products receptor (AGER or RAGE). LPA and RAGE are biomarkers of WTC-LI. Human and murine macrophages were exposed to WTC-PM, and/or LPA, and compared to controls. Supernatants were assessed for cytokines/chemokines; cell lysate immunoblots were assessed for signaling intermediates after 24 h. To explore the translatability of our in-vitro findings, we assessed serum cytokines/chemokines and metabolites of symptomatic, never-smoking WTC-exposed firefighters. Agglomerative hierarchical clustering identified phenotypes of WTC-PM-induced inflammation. WTC-PM induced GM-CSF, IL-8, IL-10, and MCP-1 in THP-1-derived macrophages and induced IL-1α, IL-10, TNF-α, and NF-κB in RAW264.7 murine macrophage-like cells. Co-exposure induced synergistic elaboration of IL-10 and MCP-1 in THP-1-derived macrophages. Similarly, co-exposure synergistically induced IL-10 in murine macrophages. Synergistic effects were seen in the context of a downregulation of NF-κB, p-Akt, -STAT3, and -STAT5b. RAGE expression after co-exposure increased in murine macrophages compared to controls. In our integrated analysis, the human cytokine/chemokine biomarker profile of WTC-LI was associated with discriminatory metabolites (fatty acids, sphingolipids, and amino acids). LPA synergistically elaborated WTC-PM’s inflammatory effects in vitro and was partly RAGE-mediated. Further research will focus on the intersection of MetSyn/PM exposure.

Keywords: lysophosphatidic acid; particulate matter exposure; RAGE; synergy

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MDPI and ACS Style

Lam, R.; Haider, S.H.; Crowley, G.; Caraher, E.J.; Ostrofsky, D.F.; Talusan, A.; Kwon, S.; Prezant, D.J.; Wang, Y.; Liu, M.; et al. Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment. Int. J. Environ. Res. Public Health 2020, 17, 4318. https://doi.org/10.3390/ijerph17124318

AMA Style

Lam R, Haider SH, Crowley G, Caraher EJ, Ostrofsky DF, Talusan A, Kwon S, Prezant DJ, Wang Y, Liu M, et al. Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment. International Journal of Environmental Research and Public Health. 2020; 17(12):4318. https://doi.org/10.3390/ijerph17124318

Chicago/Turabian Style

Lam, Rachel, Syed H. Haider, George Crowley, Erin J. Caraher, Dean F. Ostrofsky, Angela Talusan, Sophia Kwon, David J. Prezant, Yuyan Wang, Mengling Liu, and et al. 2020. "Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment" International Journal of Environmental Research and Public Health 17, no. 12: 4318. https://doi.org/10.3390/ijerph17124318

APA Style

Lam, R., Haider, S. H., Crowley, G., Caraher, E. J., Ostrofsky, D. F., Talusan, A., Kwon, S., Prezant, D. J., Wang, Y., Liu, M., & Nolan, A. (2020). Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment. International Journal of Environmental Research and Public Health, 17(12), 4318. https://doi.org/10.3390/ijerph17124318

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Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment

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