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The molecular fingerprint of lung inflammation after blunt chest trauma.

Ehrnthaller C, Flierl M, Perl M, Denk S, Unnewehr H, Ward PA, Radermacher P, Ignatius A, Gebhard F, Chinnaiyan A, Huber-Lang M - Eur. J. Med. Res. (2015)

Bottom Line: Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator).However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper).Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca(2+) channel).

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. ehrnthaller@gmx.net.

ABSTRACT

Background: After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown.

Methods: Therefore, inflammation in lung tissue following blunt chest trauma was characterized in a well-defined bilateral lung injury model. Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined.

Results: The results suggest an activation of a highly complex transcriptional program in response to chest trauma. Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator). However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper). Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca(2+) channel).

Conclusions: Taken together, the provided global perspective of the inflammatory response following blunt chest trauma could provide a molecular framework for future research in trauma pathophysiology.

No MeSH data available.


Related in: MedlinePlus

Regulated genes encoding for various cytokines or their receptors at different time-points after blunt chest trauma. Upregulation was defined as >2-fold increase of gene expression, while downregulation was considered significant when expression levels <0.5 when being compared to sham lungs. LCR-1 leucocyte chemokine receptor, TNFα tumor necrosis factor α. Displayed are mean values ± SEM
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Fig1: Regulated genes encoding for various cytokines or their receptors at different time-points after blunt chest trauma. Upregulation was defined as >2-fold increase of gene expression, while downregulation was considered significant when expression levels <0.5 when being compared to sham lungs. LCR-1 leucocyte chemokine receptor, TNFα tumor necrosis factor α. Displayed are mean values ± SEM

Mentions: In line with evidence from the literature, transcriptional programs of pro-inflammatory cytokines/chemokines and/or their corresponding receptors were found to be upregulated during the course after blunt chest trauma (Fig. 1). Gene expression for IL-1α was found to be upregulated about threefold very early after trauma (1 h) while expression of IL-1β reached significant upregulation after 12 h and persisted until 24 h. The genes for the TNFα-receptor (TNFα-R) displayed a robust upregulation 1 h through 6 h after blunt chest injury. It was found that chest trauma also seemed to decrease gene-expression levels of some pro-inflammatory cytokines and chemokines with a significant decrease of the chemokine receptor LCR-1 at 1 and 12 h after trauma (Fig. 1).Fig. 1


The molecular fingerprint of lung inflammation after blunt chest trauma.

Ehrnthaller C, Flierl M, Perl M, Denk S, Unnewehr H, Ward PA, Radermacher P, Ignatius A, Gebhard F, Chinnaiyan A, Huber-Lang M - Eur. J. Med. Res. (2015)

Regulated genes encoding for various cytokines or their receptors at different time-points after blunt chest trauma. Upregulation was defined as >2-fold increase of gene expression, while downregulation was considered significant when expression levels <0.5 when being compared to sham lungs. LCR-1 leucocyte chemokine receptor, TNFα tumor necrosis factor α. Displayed are mean values ± SEM
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4548898&req=5

Fig1: Regulated genes encoding for various cytokines or their receptors at different time-points after blunt chest trauma. Upregulation was defined as >2-fold increase of gene expression, while downregulation was considered significant when expression levels <0.5 when being compared to sham lungs. LCR-1 leucocyte chemokine receptor, TNFα tumor necrosis factor α. Displayed are mean values ± SEM
Mentions: In line with evidence from the literature, transcriptional programs of pro-inflammatory cytokines/chemokines and/or their corresponding receptors were found to be upregulated during the course after blunt chest trauma (Fig. 1). Gene expression for IL-1α was found to be upregulated about threefold very early after trauma (1 h) while expression of IL-1β reached significant upregulation after 12 h and persisted until 24 h. The genes for the TNFα-receptor (TNFα-R) displayed a robust upregulation 1 h through 6 h after blunt chest injury. It was found that chest trauma also seemed to decrease gene-expression levels of some pro-inflammatory cytokines and chemokines with a significant decrease of the chemokine receptor LCR-1 at 1 and 12 h after trauma (Fig. 1).Fig. 1

Bottom Line: Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator).However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper).Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca(2+) channel).

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. ehrnthaller@gmx.net.

ABSTRACT

Background: After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown.

Methods: Therefore, inflammation in lung tissue following blunt chest trauma was characterized in a well-defined bilateral lung injury model. Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined.

Results: The results suggest an activation of a highly complex transcriptional program in response to chest trauma. Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator). However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper). Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca(2+) channel).

Conclusions: Taken together, the provided global perspective of the inflammatory response following blunt chest trauma could provide a molecular framework for future research in trauma pathophysiology.

No MeSH data available.


Related in: MedlinePlus