Abstract
Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-κB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3774-3785 |
| Number of pages | 12 |
| Journal | Journal of Cellular and Molecular Medicine |
| Volume | 13 |
| Issue number | 9 B |
| DOIs | |
| State | Published - Sep 2009 |
| Externally published | Yes |
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Keywords
- Alpha7nAchR
- Cytokines
- Haemorrhagic shock
- HMGB1
- Inflammation
- Nicotinic receptors
- Resuscitation
- TNF
ASJC Scopus subject areas
- Cell Biology
- Molecular Medicine
Cite this
Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation. / Cai, Bolin; Chen, Fei; Ji, Yan; Kiss, Levente; de Jonge, Wouter J.; Conejero-Goldberg, Concepcion; Szabo, Csaba; Deitch, Edwin A.; Ulloa, Luis.
In: Journal of Cellular and Molecular Medicine, Vol. 13, No. 9 B, 09.2009, p. 3774-3785.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation
AU - Cai, Bolin
AU - Chen, Fei
AU - Ji, Yan
AU - Kiss, Levente
AU - de Jonge, Wouter J.
AU - Conejero-Goldberg, Concepcion
AU - Szabo, Csaba
AU - Deitch, Edwin A.
AU - Ulloa, Luis
PY - 2009/9
Y1 - 2009/9
N2 - Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-κB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.
AB - Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-κB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.
KW - Alpha7nAchR
KW - Cytokines
KW - Haemorrhagic shock
KW - HMGB1
KW - Inflammation
KW - Nicotinic receptors
KW - Resuscitation
KW - TNF
UR - http://www.scopus.com/inward/record.url?scp=77449083458&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77449083458&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2008.00550.x
DO - 10.1111/j.1582-4934.2008.00550.x
M3 - Article
VL - 13
SP - 3774
EP - 3785
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 9 B
ER -