TY - JOUR
T1 - Long-term dynamic profiling of inflammatory mediators in double-hit burn and sepsis animal models
AU - Orman, Mehmet A.
AU - Ierapetritou, Marianthi G.
AU - Berthiaume, Francois
AU - Androulakis, Ioannis P.
N1 - Funding Information:
The authors gratefully acknowledge the financial support from NIH Grant GM082974 .
PY - 2012/5
Y1 - 2012/5
N2 - Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed 2 days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10. days (0, 1, 2, 3, 4, 7 and 10. days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators' behaviors in various injury models.
AB - Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed 2 days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10. days (0, 1, 2, 3, 4, 7 and 10. days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators' behaviors in various injury models.
KW - Burn
KW - Cecal ligation and puncture
KW - Chemokines
KW - Cytokines
KW - Inflammatory response
KW - Transcription factors
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U2 - 10.1016/j.cyto.2012.01.017
DO - 10.1016/j.cyto.2012.01.017
M3 - Article
C2 - 22402033
AN - SCOPUS:84859216932
SN - 1043-4666
VL - 58
SP - 307
EP - 315
JO - Cytokine
JF - Cytokine
IS - 2
ER -