Cytokine Production Modified by System X(c)- After PM10 and Asbestos Exposure

Our plain-English summary of Cytokine Production Modified by System X(c)- After PM10 and Asbestos Exposure, by J. Overocker, J.C. Pfau (Journal of Young Investigators, 2012).

The study

• Authors: J. Overocker, J.C. Pfau
• Journal: Journal of Young Investigators
• Published: 2012;23(6):34-39
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

It has been shown that inhaled particulate matter such as air pollution and asbestos are linked to a number of immune diseases such as asthma, and Systemic Lupus Erythematosus (SLE), respectively. This research may contribute to understanding the mechanisms of how asbestos and air pollution particulate (PM10) produce oxidative stress on macrophages, as well as how the macrophages will respond to the oxidative stressors. Using Flow Cytometry, DCFDA Fluorescence, Glutamate Transport, and Cytokine Bead Array assays, we have shown that exposure to asbestos and PM10 up-regulates system x(c)- in macrophages, which reduces oxidative stress for the macrophage by providing substrates for antioxidants. The results demonstrate that asbestos, but not PM10, induces both expression and activity of system x(c)-. This led to differential cytokine production with a significantly increased expression of TNF alpha and MCP-1 for PM10 treatment but not for asbestos treatment. Inhibition of system x(c)- affected cytokine production only following asbestos exposure, further demonstrating a role for this antioxidant system in regulating immune outcomes for asbestos but not PM10. Understanding the mechanisms in which oxidative stress helps regulate macrophage responses may contribute to a better understanding of why certain diseases are brought on by asbestos and air pollution exposure.

In plain English

This was a laboratory study of macrophages, a type of immune cell, grown in culture (the RAW 264.7 cell line). The authors exposed the cells to Libby, Montana amphibole asbestos (a sample called 6-Mix) or to urban air-pollution dust (PM10), both at 35 micrograms per square centimetre. They studied an antioxidant transporter on the cells called system xc-. Both materials raised oxidative stress, a kind of chemical stress inside cells. Only the asbestos significantly increased glutamate transport, which the authors took as a sign that the transporter was active. PM10 led the cells to release two signalling proteins, TNF alpha and MCP-1. Asbestos led to TNF alpha only. A drug that blocks the transporter did not significantly change cytokine release after PM10. After asbestos, it significantly reduced both cytokines. The authors concluded that asbestos, but not PM10, activates system xc- in macrophages, and that this difference appears to cause the different cytokine responses. The article's sections disagree on some points, and this copy includes the figure captions but not the figures, so it gives no numerical levels.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: RAW 264.7 macrophage cell line grown in culture; figures report n=4 in each group; experiments replicated at least twice
• Exposure: Libby, MT amphibole asbestos ('6-Mix', from the US Geological Survey) and PM10 urban dust (National Institutes of Standards & Technology), each at 35 micrograms per square centimetre; some cells were pre-treated with the system xc- inhibitor (S)-4-CPG at 500 micromolar
• Main results:
  • In the Discussion, the authors state that only asbestos significantly increased expression of xCT, the active part of system xc- (the Results section says xCT expression increased with both materials)
  • Oxidative stress was significantly higher than in untreated cells for PM10 at the 2-hour time point and for asbestos at the 3-hour time point
  • Glutamate transport was significantly increased in asbestos-treated cells but not in PM10-treated cells
  • PM10 led to production of both TNF alpha and MCP-1; asbestos led only to TNF alpha
  • The inhibitor alone had little effect on these two cytokines
  • Blocking the transporter did not significantly change cytokine production after PM10
  • Blocking the transporter significantly reduced both MCP-1 and TNF alpha from asbestos-treated cells
  • The TNF alpha to MCP-1 ratio was significantly reduced by the inhibitor in asbestos-treated cells but not significantly changed in PM10-treated cells
• The authors' conclusion: The authors concluded that Libby 6-Mix asbestos activates system xc- in macrophages while PM10 does not, and that this difference appears to cause the different cytokine responses
• Limitations the authors state:
  • The authors acknowledge that many other factors could influence the immune (TH) responses they inferred from the two-cytokine ratio

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Cytokine, Asbestos Exposure, Oxidative Stress, Macrophage.

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