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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: Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined.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

Genes encoding for molecules involved in intracellular signaling following blunt chest trauma. Expression ratio of trauma lungs/sham lungs >2 was defined as upregulation, a ratio of <0.5 as downregulation. MAPK mitogen activated protein kinase, MKP mitogen activated protein kinase phosphatase. Displayed are mean values ± SEM
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Fig2: Genes encoding for molecules involved in intracellular signaling following blunt chest trauma. Expression ratio of trauma lungs/sham lungs >2 was defined as upregulation, a ratio of <0.5 as downregulation. MAPK mitogen activated protein kinase, MKP mitogen activated protein kinase phosphatase. Displayed are mean values ± SEM

Mentions: Trauma-induced transcriptional alterations of selected molecules involved in intracellular signaling are exhibited in Fig. 2. As early as 1 h after trauma, the G-protein coupled receptor protein reached a significant upregulation (up to threefold; Fig. 2). MAPK-6 remained significantly elevated from 1 h until 6 h post-trauma. Over the full observation period, there were various intracellular signaling molecules whose genomic expression was diminished after chest trauma (Fig. 2). E.g., expression of the inhibitory protein phosphatase was reduced 1–24 h after injury. MKP-21 showed significantly decreased levels over the whole observation period whereas for MKP-4 a trend towards elevated levels could be detected (data not shown).Fig. 2


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)

Genes encoding for molecules involved in intracellular signaling following blunt chest trauma. Expression ratio of trauma lungs/sham lungs >2 was defined as upregulation, a ratio of <0.5 as downregulation. MAPK mitogen activated protein kinase, MKP mitogen activated protein kinase phosphatase. 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

Fig2: Genes encoding for molecules involved in intracellular signaling following blunt chest trauma. Expression ratio of trauma lungs/sham lungs >2 was defined as upregulation, a ratio of <0.5 as downregulation. MAPK mitogen activated protein kinase, MKP mitogen activated protein kinase phosphatase. Displayed are mean values ± SEM
Mentions: Trauma-induced transcriptional alterations of selected molecules involved in intracellular signaling are exhibited in Fig. 2. As early as 1 h after trauma, the G-protein coupled receptor protein reached a significant upregulation (up to threefold; Fig. 2). MAPK-6 remained significantly elevated from 1 h until 6 h post-trauma. Over the full observation period, there were various intracellular signaling molecules whose genomic expression was diminished after chest trauma (Fig. 2). E.g., expression of the inhibitory protein phosphatase was reduced 1–24 h after injury. MKP-21 showed significantly decreased levels over the whole observation period whereas for MKP-4 a trend towards elevated levels could be detected (data not shown).Fig. 2

Bottom Line: Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined.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