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STAT3-dependent CXC chemokine formation and neutrophil migration in Streptococcal M1 protein-induced acute lung inflammation.

Zhang, Songen LU ; Hwaiz, Rundk LU ; Luo, Ling Tao LU ; Herwald, Heiko LU and Thorlacius, Henrik LU (2015) In American Journal of Physiology: Lung Cellular and Molecular Physiology 308(11). p.1159-1167
Abstract
Streptococcus pyogenes cause infections ranging from mild pharyngitis to severe streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, it was hypothesized that STAT3 signaling might be involved in M1 protein-evoked lung inflammation. The STAT3 inhibitor, S3I-201, was administered to male C57Bl/6 mice before i.v. challenge with M1 protein. Bronchoalveolar fluid and lung tissue were harvested for quantification of STAT3 activity, neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Levels of IL-6 and HMGB1 were determined in plasma. CXCL2-induced neutrophil chemotaxis was studied in... (More)
Streptococcus pyogenes cause infections ranging from mild pharyngitis to severe streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, it was hypothesized that STAT3 signaling might be involved in M1 protein-evoked lung inflammation. The STAT3 inhibitor, S3I-201, was administered to male C57Bl/6 mice before i.v. challenge with M1 protein. Bronchoalveolar fluid and lung tissue were harvested for quantification of STAT3 activity, neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Levels of IL-6 and HMGB1 were determined in plasma. CXCL2-induced neutrophil chemotaxis was studied in vitro. Administration of S3I-201 markedly reduced M1 protein-provoked STAT3 activity, neutrophil recruitment, edema formation and inflammatory changes in the lung. In addition, M1 protein significantly increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Treatment with S3I-201 had no effect on M1 protein-induced expression of Mac-1 on neutrophils. In contrast, inhibition of STAT3 activity greatly reduced M1 protein-induced formation of CXC chemokines in the lung. Interestingly, STAT3 inhibition markedly decreased plasma levels of IL-6 and HMGB1 in animals exposed to M1 protein. Moreover, we found that S3I-201 abolished CXCL2-induced neutrophil migration in vitro. In conclusion, these novel findings indicate that STAT3 signaling plays a key role in mediating CXC chemokine production and neutrophil infiltration in M1 protein-induced acute lung inflammation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
volume
308
issue
11
pages
1159 - 1167
publisher
American Physiological Society
external identifiers
  • pmid:25840996
  • wos:000357509200007
  • scopus:84930840247
ISSN
1522-1504
DOI
10.1152/ajplung.00324.2014
language
English
LU publication?
yes
id
226e8808-30cf-4ab9-916b-a643448bcd4d (old id 5345554)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25840996?dopt=Abstract
date added to LUP
2015-05-06 16:23:02
date last changed
2017-09-17 04:17:38
@article{226e8808-30cf-4ab9-916b-a643448bcd4d,
  abstract     = {Streptococcus pyogenes cause infections ranging from mild pharyngitis to severe streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, it was hypothesized that STAT3 signaling might be involved in M1 protein-evoked lung inflammation. The STAT3 inhibitor, S3I-201, was administered to male C57Bl/6 mice before i.v. challenge with M1 protein. Bronchoalveolar fluid and lung tissue were harvested for quantification of STAT3 activity, neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Levels of IL-6 and HMGB1 were determined in plasma. CXCL2-induced neutrophil chemotaxis was studied in vitro. Administration of S3I-201 markedly reduced M1 protein-provoked STAT3 activity, neutrophil recruitment, edema formation and inflammatory changes in the lung. In addition, M1 protein significantly increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Treatment with S3I-201 had no effect on M1 protein-induced expression of Mac-1 on neutrophils. In contrast, inhibition of STAT3 activity greatly reduced M1 protein-induced formation of CXC chemokines in the lung. Interestingly, STAT3 inhibition markedly decreased plasma levels of IL-6 and HMGB1 in animals exposed to M1 protein. Moreover, we found that S3I-201 abolished CXCL2-induced neutrophil migration in vitro. In conclusion, these novel findings indicate that STAT3 signaling plays a key role in mediating CXC chemokine production and neutrophil infiltration in M1 protein-induced acute lung inflammation.},
  author       = {Zhang, Songen and Hwaiz, Rundk and Luo, Ling Tao and Herwald, Heiko and Thorlacius, Henrik},
  issn         = {1522-1504},
  language     = {eng},
  number       = {11},
  pages        = {1159--1167},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {STAT3-dependent CXC chemokine formation and neutrophil migration in Streptococcal M1 protein-induced acute lung inflammation.},
  url          = {http://dx.doi.org/10.1152/ajplung.00324.2014},
  volume       = {308},
  year         = {2015},
}