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Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways

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Abstract

Objective and design

The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages.

Materials and methods

The release of nitric oxide (NO), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1β, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay.

Results

MHNA significantly inhibited the release of NO, IL-1β and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1β and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-κB DNA-binding activity and NF-κB transcriptional activity as well as IκB-α degradation and NF-κB translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA.

Conclusions

MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-κB and MAPKs signaling pathways activation.

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Abbreviations

COX-2:

Cyclooxygenase-2

EMSA:

Electrophoretic mobility shift assay

ERK:

Extracellular signal-regulated kinases

iNOS:

Inducible nitric oxide synthase

IκB:

Inhibitory kappa B

IL-1β:

Interleukin-1beta

IL-6:

Interleukin-6

JNK:

c-Jun N-terminal kinases

LPS:

Lipopolysaccharide

MAPKs:

Mitogen-activated protein kinases

NO:

Nitric oxide

NF-κB:

Nuclear factor kappa B

PGE2 :

Prostaglandin E2

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

This work was supported by grants from the Science and Technology Bureau of Guangzhou (2006Z1-E6021).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Jun-Yan Zhang, Hong Jin, Guang-Fa Wang, Peng-Jiu Yu, Shao-Yu Wu, Zheng-Guang Zhu, Zhong-Huang Li, Yuan-Xin Tian, Wei Xu, Jia-Jie Zhang & Shu-Guang Wu

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  1. Jun-Yan Zhang
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  2. Hong Jin
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Correspondence to Jia-Jie Zhang or Shu-Guang Wu.

Additional information

Responsible Editor: Liwu Li.

Jun-Yan Zhang and Hong Jin contributed equally to this work.

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Zhang, JY., Jin, H., Wang, GF. et al. Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways. Inflamm. Res. 60, 851–859 (2011). https://doi.org/10.1007/s00011-011-0345-2

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