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Open Access 01-09-2013 | Original Contribution

Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation

Authors: P. Markowski, O. Boehm, L. Goelz, A. L. Haesner, H. Ehrentraut, K. Bauerfeld, N. Tran, K. Zacharowski, C. Weisheit, P. Langhoff, M. Schwederski, T. Hilbert, S. Klaschik, A. Hoeft, G. Baumgarten, R. Meyer, P. Knuefermann

Published in: Basic Research in Cardiology | Issue 5/2013

Abstract

The aim of the study was to investigate whether pre-conditioning with CpG-oligodeoxynucleotides (CpG-ODN) may change cardiac ischemia/reperfusion (I/R)-dependent inflammation and modulates infarct size and cardiac performance. WT and TLR9-deficient mice were pre-treated with 1668-, 1612- and H154-thioate or D-Gal as control. Priming with 1668-thioate significantly induced inflammatory mediators in the serum and a concomitant increase of immune cells in the blood and spleen of WT mice. Furthermore, it induced myocardial pattern recognition receptors and pro-inflammatory cytokines peaking 2 h after priming and a continuous increase of IL-10. 16 h after pre-conditioning, myocardial ischemia was induced for 1 h. Infarct size determined after 24 h of I/R was reduced by 75 % due to pre-conditioning with 1668-thioate but not in the other groups. During reperfusion, cytokine expression in 1668-thioate primed mice increased further with IL-10 exceeding the other mediators by far. These changes were observed neither in animals pre-treated with 1612- or H154-thioate nor in TLR9-deficient mice. The 1668-thioate-dependent increase of IL-10 was further supported by results of a micro-array analysis 3 h after begin of reperfusion. Block of IL-10 signaling increased I/R size and prevented influence of priming. In the group pre-treated with 1668-thioate, cardiac function was preserved 24 h, 14 days and 28 days after I/R, whereas animals without pre-conditioning exhibited impaired heart function 24 h and 14 days after I/R. The excessive 1668-thioate-dependent IL-10 up-regulation during pre-conditioning and after I/R seems to be the key factor for reducing infarct size and improving cardiac function. This is in agreement with the finding that IL-10 block prevents cardioprotection by pre-conditioning.

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Title: Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation
Authors: P. Markowski
O. Boehm
L. Goelz
A. L. Haesner
H. Ehrentraut
K. Bauerfeld
N. Tran
K. Zacharowski
C. Weisheit
P. Langhoff
M. Schwederski
T. Hilbert
S. Klaschik
A. Hoeft
G. Baumgarten
R. Meyer
P. Knuefermann
Publication date: 01-09-2013
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2013
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-013-0376-7

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Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation

Abstract

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