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GSK-3β inhibitor modulates TLR2/NF-κB signaling following myocardial ischemia-reperfusion

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Abstract

Objective

The present study defines the expression of Toll-like Receptor 2 (TLR2), and the modulatory role of Glycogen synthase kinase (GSK)-3β inhibitor on TLR2/Nuclear Factor-kappa B (NF-κB) signaling following myocardial ischemia-reperfusion (MI-R) injury in rats.

Methods

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to analyze the presence and quantity of TLR2 mRNA and protein. Tumor necrosis factor (TNF)-α mRNA and interleukin-6 (IL-6) mRNA were analyzed by RT-PCR. The activation of NF-κB was detected by Western Blot and the myocardial infarct size by Evans blue-TTC staining.

Results

Following 30 min of myocardial ischemia, a significant up-regulation of TLR2 mRNA was revealed by RT-PCR from 1 to 24 h post reperfusion. IHC demonstrated high protein expression levels of TLR2. Administration of the GSK-3β inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8) 5 min prior to reperfusion following 1 h reperfusion down-regulated mRNA levels of TLR2 and downstream proinflammatory cytokines (P < 0.05 vs. MI-R), decreased the activity of NF-κB and the size of the myocardial infarct (P < 0.05 vs. MI-R).

Conclusion

Our results demonstrate that TLR2 and its signaling components are activated by MI-R. TDZD-8 administration attenuates TLR2/NF-κB signaling, suggesting a possible mechanism whereby GSK-3β inhibition improves the outcome of MI-R.

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Acknowledgment

The authors thank Dr. Ling Tao (Department of Cardiology, Xi Jing Hospital, Fourth Military Medical University) for her help and careful revision of this article.

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Authors and Affiliations

  1. Department of Cardiology, Xi Jing Hospital, Fourth Military Medical University, Xi’an, China

    Hao-Kao Gao, Zhong Yin, Rong-Qing Zhang, Jun Zhang & Hai-Chang Wang

  2. Department of Physiology, Fourth Military Medical University, Xi’an, China

    Feng Gao

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  1. Hao-Kao Gao
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  2. Zhong Yin
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  3. Rong-Qing Zhang
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  4. Jun Zhang
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  5. Feng Gao
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Correspondence to Hai-Chang Wang.

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Responsible Editor: S. Stimpson.

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Gao, HK., Yin, Z., Zhang, RQ. et al. GSK-3β inhibitor modulates TLR2/NF-κB signaling following myocardial ischemia-reperfusion. Inflamm. Res. 58, 377–383 (2009). https://doi.org/10.1007/s00011-009-0002-1

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  • DOI: https://doi.org/10.1007/s00011-009-0002-1

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