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Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung

Zhang, Songen LU ; Rahman, Milladur LU ; Zhang, Su LU ; Qi, Zhongquan LU ; Herwald, Heiko LU and Thorlacius, Henrik LU (2011) In American Journal of Physiology: Lung Cellular and Molecular Physiology 300(6). p.930-939
Abstract
Zhang S, Rahman M, Zhang S, Qi Z, Herwald H, Thorlacius H. Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung. Am J Physiol Lung Cell Mol Physiol 300: L930-L939, 2011. First published March 25, 2011; doi:10.1152/ajplung.00422.2010.-Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung injury. Statins exert beneficial effects in septic patients although the mechanisms remain elusive. This study examined effects of simvastatin on M1 protein-provoked pulmonary inflammation and tissue injury. Male C57BL/6 mice were pretreated with simvastatin or a CXCR2 antagonist before M1 protein challenge. Bronchoalveolar fluid and lung tissue... (More)
Zhang S, Rahman M, Zhang S, Qi Z, Herwald H, Thorlacius H. Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung. Am J Physiol Lung Cell Mol Physiol 300: L930-L939, 2011. First published March 25, 2011; doi:10.1152/ajplung.00422.2010.-Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung injury. Statins exert beneficial effects in septic patients although the mechanisms remain elusive. This study examined effects of simvastatin on M1 protein-provoked pulmonary inflammation and tissue injury. Male C57BL/6 mice were pretreated with simvastatin or a CXCR2 antagonist before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for determination of neutrophil infiltration, formation of edema, and CXC chemokines. Flow cytometry was used to determine Mac-1 expression on neutrophils. Gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative RT-PCR. M1 protein challenge caused massive infiltration of neutrophils, edema formation, and production of CXC chemokines in the lung as well as upregulation of Mac-1 on circulating neutrophils. Simvastatin reduced M1 protein-induced infiltration of neutrophils and edema in the lung. In addition, M1 protein-induced Mac-1 expression on neutrophils was abolished by simvastatin. Furthermore, simvastatin markedly decreased pulmonary formation of CXC chemokines and gene expression of CXC chemokines in alveolar macrophages. Moreover, the CXCR2 antagonist reduced M1 protein-induced neutrophil expression of Mac-1 and accumulation of neutrophils as well as edema formation in the lung. These novel findings indicate that simvastatin is a powerful inhibitor of neutrophil infiltration in acute lung damage triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil recruitment appears related to reduced pulmonary generation of CXC chemokines. Thus, simvastatin may be a useful tool to ameliorate acute lung injury in streptococcal infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
statins, CXC chemokines, neutrophils, lung, sepsis
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
volume
300
issue
6
pages
930 - 939
publisher
American Physiological Society
external identifiers
  • wos:000291204100013
  • scopus:79958219008
ISSN
1522-1504
DOI
10.1152/ajplung.00422.2010
language
English
LU publication?
yes
id
8d9ac164-5f49-4a96-9ab7-be172c267654 (old id 1985660)
date added to LUP
2011-07-01 09:01:37
date last changed
2017-01-01 03:40:33
@article{8d9ac164-5f49-4a96-9ab7-be172c267654,
  abstract     = {Zhang S, Rahman M, Zhang S, Qi Z, Herwald H, Thorlacius H. Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung. Am J Physiol Lung Cell Mol Physiol 300: L930-L939, 2011. First published March 25, 2011; doi:10.1152/ajplung.00422.2010.-Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung injury. Statins exert beneficial effects in septic patients although the mechanisms remain elusive. This study examined effects of simvastatin on M1 protein-provoked pulmonary inflammation and tissue injury. Male C57BL/6 mice were pretreated with simvastatin or a CXCR2 antagonist before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for determination of neutrophil infiltration, formation of edema, and CXC chemokines. Flow cytometry was used to determine Mac-1 expression on neutrophils. Gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative RT-PCR. M1 protein challenge caused massive infiltration of neutrophils, edema formation, and production of CXC chemokines in the lung as well as upregulation of Mac-1 on circulating neutrophils. Simvastatin reduced M1 protein-induced infiltration of neutrophils and edema in the lung. In addition, M1 protein-induced Mac-1 expression on neutrophils was abolished by simvastatin. Furthermore, simvastatin markedly decreased pulmonary formation of CXC chemokines and gene expression of CXC chemokines in alveolar macrophages. Moreover, the CXCR2 antagonist reduced M1 protein-induced neutrophil expression of Mac-1 and accumulation of neutrophils as well as edema formation in the lung. These novel findings indicate that simvastatin is a powerful inhibitor of neutrophil infiltration in acute lung damage triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil recruitment appears related to reduced pulmonary generation of CXC chemokines. Thus, simvastatin may be a useful tool to ameliorate acute lung injury in streptococcal infections.},
  author       = {Zhang, Songen and Rahman, Milladur and Zhang, Su and Qi, Zhongquan and Herwald, Heiko and Thorlacius, Henrik},
  issn         = {1522-1504},
  keyword      = {statins,CXC chemokines,neutrophils,lung,sepsis},
  language     = {eng},
  number       = {6},
  pages        = {930--939},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung},
  url          = {http://dx.doi.org/10.1152/ajplung.00422.2010},
  volume       = {300},
  year         = {2011},
}