In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on <i>COX-2</i> and <i>IL-8</i> gene expression

Arashiro, Maiko; Lin, Ying-Hsuan; Sexton, Kenneth G.; Zhang, Zhenfa; Jaspers, Ilona; Fry, Rebecca C.; Vizuete, William G.; Gold, Avram; Surratt, Jason D.

doi:https://doi.org/10.5194/acp-16-14079-2016

Articles | Volume 16, issue 22

https://doi.org/10.5194/acp-16-14079-2016

© Author(s) 2016. This work is distributed under
the Creative Commons Attribution 3.0 License.

https://doi.org/10.5194/acp-16-14079-2016

© Author(s) 2016. This work is distributed under
the Creative Commons Attribution 3.0 License.

Articles | Volume 16, issue 22

Research article

|

15 Nov 2016

Research article |

| 15 Nov 2016

In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on COX-2 and IL-8 gene expression

Maiko Arashiro, Ying-Hsuan Lin, Kenneth G. Sexton, Zhenfa Zhang, Ilona Jaspers, Rebecca C. Fry, William G. Vizuete, Avram Gold, and Jason D. Surratt

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Final revised paper (published on 15 Nov 2016)
Preprint (discussion started on 17 May 2016)

Interactive discussion

Status: closed

AC: Author comment | RC: Referee comment | SC: Short comment | EC: Editor comment

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- Supplement

RC1: 'Toxicity of SOA is an important scientific issue', Anonymous Referee #1, 08 Jun 2016
- AC1: 'Reply to Reviewer 1 Comments', Jason Surratt, 24 Aug 2016
RC2: 'is Isoprene SOA toxic?', Anonymous Referee #2, 14 Jun 2016
- AC2: 'Reply to Reviewer 2 Comments', Jason Surratt, 24 Aug 2016
RC3: 'comments', Anonymous Referee #3, 16 Jun 2016
- AC3: 'Reply to Reviewer 3 Comments', Jason Surratt, 24 Aug 2016

Peer-review completion

AR: Author's response | RR: Referee report | ED: Editor decision

AR by Jason Surratt on behalf of the Authors (24 Aug 2016) Author's response Manuscript

ED: Reconsider after major revisions (25 Aug 2016) by Yinon Rudich

AR by Jason Surratt on behalf of the Authors (12 Sep 2016) Author's response Manuscript

ED: Referee Nomination & Report Request started (12 Sep 2016) by Yinon Rudich

RR by Anonymous Referee #3 (19 Sep 2016)

RR by Anonymous Referee #1 (22 Sep 2016)

RR by Anonymous Referee #2 (24 Sep 2016)

Suggestions for revision or reasons for rejection

The lack of context of this work remains largely unaddressed. The authors have modified the paper slightly, now asserting that this work is more exploratory in nature and that it shows more research in isoprene SOA toxicity is warranted. All three reviewers, in some form or other, have raised the issue questioning how isoprene SOA causes a potentially adverse health response, or put another way, what is the significance of increases in il-8 and cox-2 genes when exposed to isoprene SOA The author’s answer to this question is essentially based on their other reported research. The logic put forward in this paper is summarized in lines 400 to 410 (copied below, next paragraph)

"The mechanism by which isoprene-SOA causes elevation of the inflammatory markers  IL-8 and COX-2 is not yet fully understood. However, recent work from our laboratory using the  acellular dithiothreitol (DTT) assay demonstrated that isoprene-derived SOA have equal or  greater ROS generation potential than diesel exhaust PM (Kramer et al., 2016; Rattanavaraha et  al., 2011). High levels of ROS in cells can overwhelm the antioxidant defense and lead to  cellular oxidative stress (Bowler and Crapo, 2002; Li et al., 2003; Sies, 1991). Following the  discovery of the potential importance of isoprene-SOA in generating ROS, Lin et al. (2016)  showed that isoprene-SOA formed from the reactive uptake of epoxides alters levels of oxidative  stress-associated genes, including COX-2 in human lung cells. Oxidative stress caused by ROS  plays a major role in lung inflammation and the induction of oxidative stress can lead to IL-8  expression (Tao et al., 2003; Yan et al., 2015). "

The logic is: Diesel is a known toxic aerosol component (implicitly assumed), and ROS (as measured by the DTT assay) is linked to oxidative stress, which is linked to various adverse health endpoints. Since isoprene SOA has equal of higher DTT per mass activities than diesel, and DTT assay is a measure of aerosol oxidative potential, isoprene may be toxic through an oxidative stress route. The problem with this logic is that it all hinges on isoprene SOA being more toxic than diesel, as reported by (Kramer et al., 2016; Rattanavaraha et al., 2011). These papers indeed show this, but the comparison in these two papers is flawed because, for some reason, the diesel DTT per mass reported in Kramer et al., and Rattanavaraha et al, (note, that Rattanavaraha et al appears to simply reuses Kramer et al data, so it all comes down to Kramer) is vastly lower (by about a factor of 10) than what others have reported in both chamber and ambient studies [Bates et al., 2015; Charrier et al., 2015; McWhinney et al., 2013]. (Note, more papers on ambient DTT per mass activities in locations highly impacted by vehicle emissions also exist, but I have not included them here).

The response of the authors to this issue raised in the first review was that Bates et al isoprene DTT per mass was based on AMS PMF data and so the isoprene SOA was a different form than the isoprene SOA in this experiment. But that is not the issue. Bates also gives low DTT per mass activities for Other OA (ie, expected to be mainly biogenic SOA). The issue is not DTT per mass for isoprene, there is actually some agreement on this, the issue is why is Rattanavaraha DTT per mass for diesel so low relative to other studies? By only citing their own work and ignoring other published data the authors have made a substantial flaw in reasoning and also give a biased interpretation. The line, “our laboratory using the  acellular dithiothreitol (DTT) assay demonstrated that isoprene-derived SOA have equal or  greater ROS generation potential than diesel exhaust PM.” is factually correct since the citation is limited to their work, but is known to be much more complicated than they knowledge. It seems to be defined narrowly here simply to support the premise of this paper. This issue must be rectified before publication.

Bates, J. T., R. J. Weber, J. Abrams, V. Verma, T. Fang, M. Klein, M. J. Strckland, S. Sarnat, H. Chang, J. A. Mulholland, P. E. Tolbert, and A. G. Russell (2015), Reactive Oxygen Species in Atmospheric Particulate Matter Suggest a Link to Cardiorespiratory Effects, Envir. Sci. Technol, 49, 13605-13612

Charrier, J. G., N. K. Richards-Henderson, K. J. Bein, A. S. McFall, A. S. Wexler, and C. Anastasio (2015), Oxidant production from source-oriented particulate matter – Part 1: Oxidative potential using the dithiothreitol (DTT) assay, Atmos. Chem. Phys., 15, 2327-2340.

McWhinney, R. D., K. Badali, J. Liggio, S.-M. Li, and J. P. D. Abbatt (2013), Filterable redox cycling activity: A comparison between diesel exhaust particles and secondary aerosol constituents, Environ. Sci. Technol., 47, 3362-3369.

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ED: Reconsider after minor revisions (Editor review) (24 Sep 2016) by Yinon Rudich

AR by Anna Mirena Feist-Polner on behalf of the Authors (10 Oct 2016) Author's response

ED: Publish as is (18 Oct 2016) by Yinon Rudich

Short summary

Atmospheric oxidation of isoprene in the presence of acidic sulfate aerosol yields substantial SOA. Potential adverse health effects resulting from exposure to this aerosol type are largely unknown. Measurements of gene expression of known inflammatory biomarkers interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) in exposed human lung cells at the air–liquid interface showed that a dose of 0.067 μg cm⁻² of isoprene SOA leads to statistically significant increases in IL-8 and COX-2 mRNA levels.