• Qing Liu, Junfeng Wang, Qiaoli Liang, Dawei Wang, Yi Luo, Jianping Li, Joseph S Janicki, and Daping Fan.
• Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
• Exp. Biol. Med. (Maywood). 2014 Mar 1; 239 (3): 376-84.

AbstractMyocardial ischemia-reperfusion (MIR) injury is characterized by a rapid increase in cytokines and chemokines and an infiltration of inflammatory cells. Toll-like receptors (TLRs) 2 and 4 mediate these inflammatory responses. Herein we investigated the ability of Sparstolonin B (SsnB), a new selective TLR2/4 antagonist, to inhibit the TLR2/4-mediated inflammatory responses during cardiomyocyte hypoxia-reoxygenation injury as well as the responsible mechanisms. Lactate dehydrogenase (LDH) assay was performed to measure the cytotoxicity of SsnB on H9c2 cardiomyocytes. Quantitative real-time PCR (qRT-PCR) confirmed that TLR2 and TLR4 expression was elevated during hypoxia-reoxygenation, and that their up-regulation in cardiomyocytes was significantly inhibited by SsnB (P < 0.05). Both the mRNA and protein levels of monocyte chemotactic protein-1 and high mobility group box 1 were up-regulated during hypoxia-reoxygenation and were significantly attenuated by SsnB (P < 0.05). Next we found that extracellular signal-regulated kinase 1 or 2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) signaling pathways were activated during hypoxia-reoxygenation and SsnB significantly inhibited their activation (P < 0.05). Moreover, transwell migration assays revealed that the migration of mouse macrophages to hypoxia-reoxygenation injured cardiomyocytes was significantly reduced by SsnB (P < 0.05). In conclusion, our data indicate that the new selective TLR2 and TLR4 antagonist, SsnB, can substantially attenuate hypoxia-reoxygenation-induced inflammation of cardiomyocytes via inhibiting ERK1/2 and JNK signaling pathways. Accordingly, SsnB has the potential to serve as a therapeutic agent for the prevention of MIR injury.

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