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Urban particulate matter activates Akt in human lung cells

  • Organ Toxicity and Mechanisms
  • Published:
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Abstract

The normally picturesque Cache Valley in northern Utah is frequently reported to have the worst particulate (PM) air pollution in the United States. Numerous epidemiological studies conducted elsewhere have associated PM exposure to a variety of cardiovascular diseases and early mortality. We have previously shown that Cache Valley PM (CVPM) is pro-inflammatory, through a variety of mechanisms involving the release of inflammatory cytokines, unfolded protein response, ER stress, and C-reactive protein (CRP). This study was undertaken to determine whether Cache Valley PM (CVPM) would activate Akt, an upstream mechanism common to these events. Human lung (BEAS-2B) cells were treated with either fine (PM2.5) or coarse (PM10) particles (12.5 and 25 μg/ml) for periods up to 24 h. PM-exposed cells exhibited Akt activation as evidenced by phosphorylation at Thr308 and Ser473. Events downstream of Akt activation such as NF-κB activation were observed at 1 and 24 h, but IκB phosphorylation occurred only at 24 h, indicating that mechanisms of PM-mediated NF-κB activation are time dependent. Akt and NF-κB related inflammatory cytokine IL-1α, and IL-6 and the chemokine IL-8 were upregulated in treated cells at 6 and 24 h. The calpain inhibitor leupeptin limited Akt phosphorylation to Ser473 and reduced release of IL-1α, IL-6, and IL-8, indicating that calpain or similar protease(s) are involved in PM-induced activation of Akt and subsequent release of inflammatory cytokines. Our data indicate that PM activates Akt, which may play a role in the pro-inflammatory response to PM exposure.

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Acknowledgments

The authors thank Dr. John R. Stevens for the helpful suggestions. This work was supported in part by a generous gift from the Marriner S. Eccles Foundation, a pilot project of the National Children’s Study, and by the Utah Agricultural Experiment Station. Portions of this work were presented at the Society of Toxicology annual conference March 2009 in Baltimore, MD.

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Authors and Affiliations

  1. Graduate Toxicology Program, Department of Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4620 Old Main Hill, Logan, UT, 84322, USA

    Todd L. Watterson, Brett Hamilton & Roger A. Coulombe Jr.

  2. Department of Civil and Environmental Engineering, Utah State University, Logan, UT, 84322, USA

    Randy S. Martin

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  1. Todd L. Watterson
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  2. Brett Hamilton
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  4. Roger A. Coulombe Jr.
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Correspondence to Roger A. Coulombe Jr..

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Watterson, T.L., Hamilton, B., Martin, R.S. et al. Urban particulate matter activates Akt in human lung cells. Arch Toxicol 86, 121–135 (2012). https://doi.org/10.1007/s00204-011-0739-5

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