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Molecular and Cellular Biochemistry

, Volume 397, Issue 1–2, pp 109–116 | Cite as

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

  • Jae-Won Lee
  • Jae-Hyun Kwon
  • Man Sup Lim
  • Hee Jae Lee
  • Sung-Soo Kim
  • So Young Lim
  • Wanjoo Chun
Article

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.

Keywords

3,4,5-Trihydroxycinnamic acid Heme oxygenase-1 Lipopolysaccharide Sepsis Kidney 

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

Notes

Acknowledgments

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

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jae-Won Lee
    • 1
  • Jae-Hyun Kwon
    • 1
  • Man Sup Lim
    • 1
  • Hee Jae Lee
    • 1
  • Sung-Soo Kim
    • 1
  • So Young Lim
    • 2
  • Wanjoo Chun
    • 1
  1. 1.Department of Pharmacology, College of MedicineKangwon National UniversityChuncheonKorea
  2. 2.Department of Anesthesiology and Pain Medicine, College of MedicineHallym UniversityChuncheonKorea

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