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3,4,5-Trihydroxycinnamic acid increases heme-oxygenase-1 (HO-1) and decreases macrophage infiltration in LPS-induced septic kidney

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Abstract

We previously demonstrated that 3,4,5-trihydorxycinnamic acid (THC), a derivative of hydroxycinnamic acids, possesses protective effect in lipopolysaccharide (LPS)-induced endotoxemia models. However, the effects of THC in LPS-induced septic kidney are still unclear. Therefore, the present study was carried out to examine the effects of THC in LPS-challenged septic kidney using mesangial cell line and Balb/c mice. THC pretreatment effectively inhibited LPS-induced macrophage infiltration and the secretion of pro-inflammatory cytokines in the kidney of LPS-challenged animals. Pretreatment of rat mesangial cells with THC significantly attenuated LPS-induced PGE2 production and COX-2 expression. THC also significantly suppressed LPS-induced expression of MCP-1 in LPS-activated septic kidney and rat mesangial cells. In addition, THC significantly attenuated LPS-induced degradation of IκB-α in LPS-induced rat mesangial cells. THC also increased the expression of heme oxygenase-1 (HO-1) in LPS-challenged septic kidney and mesangial cells. Multiple signaling pathways including p38 and AKT have been observed to be involved in the THC-induced activation of HO-1 expression. The present data clearly demonstrate that THC protects LPS-challenged septic kidney by decreasing macrophage infiltration and increasing HO-1 expression, suggesting that THC might be a valuable therapeutic agent for compromised kidney in sepsis.

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Abbreviations

THC:

3,4,5-Trihydroxycinnamic acid

LPS:

Lipopolysaccharide

iNOS:

Inducible nitric oxide synthase

COX-2:

Cyclooxygenase-2

PGE2:

Prostaglandin E2

NF-κB:

Nuclear factor kappa B

HO-1:

Heme oxygenase-1

MCP-1:

Monocyte chemoattractant protein-1

TNF-α:

Tumor necrosis factor α

MAPK:

Mitogen-activated protein kinase

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Acknowledgments

This study was supported by 2014 Research Grant from Kangwon National University (C1010826-01-01).

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, Korea

    Jae-Won Lee, Jae-Hyun Kwon, Man Sup Lim, Hee Jae Lee, Sung-Soo Kim & Wanjoo Chun

  2. Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon, Kangwon, 200-704, Korea

    So Young Lim

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  1. Jae-Won Lee
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  2. Jae-Hyun Kwon
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Correspondence to Wanjoo Chun.

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Lee, JW., Kwon, JH., Lim, M.S. et al. 3,4,5-Trihydroxycinnamic acid increases heme-oxygenase-1 (HO-1) and decreases macrophage infiltration in LPS-induced septic kidney. Mol Cell Biochem 397, 109–116 (2014). https://doi.org/10.1007/s11010-014-2177-1

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