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Starzl R, Wolfram D, Zamora R, et al. Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling. Front Immunol. 2015;6:587doi: 10.3389/fimmu.2015.00587.
Starzl, R., Wolfram, D., Zamora, R., Jefferson, B., Barclay, D., Ho, C., Gorantla, V., Brandacher, G., Schneeberger, S., Andrew Lee, W. P., Carbonell, J., & Vodovotz, Y. (2015). Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling. Frontiers in immunology, 6587. https://doi.org/10.3389/fimmu.2015.00587
Starzl, Ravi, et al. "Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling." Frontiers in immunology vol. 6 (2015): 587. doi: https://doi.org/10.3389/fimmu.2015.00587
Starzl R, Wolfram D, Zamora R, Jefferson B, Barclay D, Ho C, Gorantla V, Brandacher G, Schneeberger S, Andrew Lee WP, Carbonell J, Vodovotz Y. Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling. Front Immunol. 2015 Nov 20;6:587. doi: 10.3389/fimmu.2015.00587. eCollection 2015. PMID: 26635801; PMCID: PMC4653302.
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Front Immunol. 2015 Nov 20;6:587. doi: 10.3389/fimmu.2015.00587. eCollection 2015.

Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling.

Frontiers in immunology

Ravi Starzl, Dolores Wolfram, Ruben Zamora, Bahiyyah Jefferson, Derek Barclay, Chien Ho, Vijay Gorantla, Gerald Brandacher, Stefan Schneeberger, W P Andrew Lee, Jaime Carbonell, Yoram Vodovotz

Affiliations

  1. Language Technologies Institute, Carnegie Mellon University , Pittsburgh, PA , USA ; Department of Plastic and Reconstructive Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Department of Plastic and Reconstructive Surgery, Johns Hopkins Medicine , Baltimore, MD , USA.
  2. Department of Plastic and Reconstructive Surgery, Innsbruck Medical University , Innsbruck , Austria.
  3. Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, PA , USA.
  4. Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA.
  5. Department of Biological Sciences, Carnegie Mellon University , Pittsburgh, PA , USA.
  6. Department of Plastic and Reconstructive Surgery, University of Pittsburgh , Pittsburgh, PA , USA.
  7. Department of Plastic and Reconstructive Surgery, Johns Hopkins Medicine , Baltimore, MD , USA.
  8. Language Technologies Institute, Carnegie Mellon University , Pittsburgh, PA , USA.

PMID: 26635801 PMCID: PMC4653302 DOI: 10.3389/fimmu.2015.00587

Abstract

BACKGROUND: Trauma often cooccurs with cardiac arrest and hemorrhagic shock. Skin and muscle injuries often lead to significant inflammation in the affected tissue. The primary mechanism by which inflammation is initiated, sustained, and terminated is cytokine-mediated immune signaling, but this signaling can be altered by cardiac arrest. The complexity and context sensitivity of immune signaling in general has stymied a clear understanding of these signaling dynamics.

METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that advanced numerical and biological function analysis methods would help elucidate the inflammatory response to skin and muscle wounds in rats, both with and without concomitant shock. Based on the multiplexed analysis of inflammatory mediators, we discerned a differential interleukin (IL)-1α and IL-18 signature in skin vs. muscle, which was suggestive of inflammasome activation in the skin. Immunoblotting revealed caspase-1 activation in skin but not muscle. Notably, IL-1α and IL-18, along with caspase-1, were greatly elevated in the skin following cardiac arrest, consistent with differential inflammasome activation.

CONCLUSION/SIGNIFICANCE: Tissue-specific activation of caspase-1 and the NLRP3 inflammasome appear to be key factors in determining the type and severity of the inflammatory response to tissue injury, especially in the presence of severe shock, as suggested via data-driven modeling.

Keywords: Inflammasome; cardiac arrest and trauma; computational modeling; data driven modeling; hemorrhagic shock; immunoregulatory; inflammatory mediators; localized tissue injury

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