Document Detail

Preconditioning by toll-like receptor 2 agonist Pam3CSK4 reduces CXCL1-dependent leukocyte recruitment in murine myocardial ischemia/reperfusion injury.
MedLine Citation:
PMID:  20081527     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To test whether preconditioning with a toll-like receptor (TLR) 2 agonist protects against myocardial ischemia and reperfusion by interfering with chemokine CXCL1 release from cardiomyocytes. DESIGN: C3H mice were challenged with vehicle or synthetic TLR2 agonist Pam3Cys-Ser-Lys4 (Pam3CSK4; 1 mg/kg) 24 hrs before myocardial ischemia (20 mins) and reperfusion (2 hrs or 24 hrs). Infarct size, troponin T release, and leukocyte recruitment were quantified. In murine cardiomyocytes (HL-1), we studied the expression/activation profile of TLR2 in response to stimulation with Pam3CSK4 (0.01-1 mg/mL). Furthermore, we studied the chemokine ligand 1 (CXCL1) response to Pam3CSK4 and ischemia/reperfusion in vivo and in vitro. SETTING: University hospital research laboratory. SUBJECTS: Anesthetized male mice and murine cardiomyocytes. MEASUREMENTS AND MAIN RESULTS: Preconditioning by Pam3CSK4 reduced infarct size and troponin T release. This was accompanied by a decreased recruitment of leukocytes into the ischemic area and an improved cardiac function. In HL-1 cells, TLR2 activation amplified the expression of the receptor in a time-dependent manner and led to CXCL1 release in a concentration-dependent manner. Preconditioning by Pam3CSK4 impaired CXCL1 release in response to a second inflammatory stimulus in vivo and in vitro. CONCLUSIONS: Preconditioning by TLR2 agonist Pam3CSK4 reduces myocardial infarct size after myocardial ischemia/reperfusion. One of the mechanisms involved is a diminished chemokine release from cardiomyocytes, which subsequently limits leukocyte infiltration.
Jan Mersmann; Reinhard Berkels; Paula Zacharowski; Nguyen Tran; Alexander Koch; Kazuma Iekushi; Stefanie Dimmeler; Tiago F Granja; Olaf Boehm; William C Claycomb; Kai Zacharowski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-19     Completed Date:  2010-03-15     Revised Date:  2010-06-01    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  903-9     Citation Subset:  AIM; IM    
Clinic of Anesthesiology, Intensive Care Medicine, and Pain Management, JW Goethe University, Frankfurt, Germany.
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MeSH Terms
Cell Line
Chemokine CXCL1 / antagonists & inhibitors,  physiology*
Chemokines / metabolism
Dose-Response Relationship, Drug
Ischemic Preconditioning, Myocardial*
Leukocytes / immunology*
Lipopeptides / pharmacology*
Mice, Inbred C3H
Myocardial Infarction / immunology
Myocardial Reperfusion Injury / genetics*,  immunology*
Myocytes, Cardiac / drug effects*,  immunology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  genetics
Toll-Like Receptor 2 / agonists*,  genetics*
Troponin T / metabolism
Reg. No./Substance:
0/Chemokine CXCL1; 0/Chemokines; 0/Cxcl1 protein, mouse; 0/Lipopeptides; 0/Pam(3)CSK(4) peptide; 0/RNA, Messenger; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2; 0/Troponin T
Comment In:
Crit Care Med. 2010 Mar;38(3):1003-4   [PMID:  20168168 ]
Erratum In:
Crit Care Med. 2010 Jun;38(6):1509

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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