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Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect

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Abstract

ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the molecular mechanism underlying the anti-inflammatory properties of AH. Treatment with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1β, inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH inhibited LPS-induced nuclear factor-κB (NFκB) DNA-binding activity. Using transfection assay and measurement of an NFκB-sensitive promoter region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS-induced NFκB transcription activity in 293T cells. AH significantly blocked LPS-induced NFκB activation in TLR4-transfected cells. Taken together, our data indicated that anti-inflammatory properties of AH resulted from the inhibition of proinflammatory cytokines and enzyme production via the TLR4/NFκB signaling pathway.

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Acknowledgments

The research was supported by the Public Welfare & Safety Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology (20120006545); the Chinese National Natural Science Fund (30973627); and a grant from Shandong Province of China (No. ZR2009CZ016).

Conflict of interest

The authors have declared that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, South Korea

    Xinying Yang, Xuelian Tang & Hyun Park

  2. Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, Ocean University of China, Qingdao, 266002, China

    Guojian Zhang, Jieying Jiao, Tianjiao Zhu, Dehai Li & Qianqun Gu

  3. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Xinying Yang

  4. Department of Aquaculture, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China

    Xuelian Tang

  5. College of Pharmacy, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea

    Sung Yeon Kim

  6. Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, South Korea

    Joo Young Lee

  7. Department of Oriental Medicine, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea

    Yong Gab Yun

Authors
  1. Xinying Yang
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  2. Guojian Zhang
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  8. Dehai Li
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  9. Yong Gab Yun
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  10. Qianqun Gu
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  11. Hyun Park
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Corresponding authors

Correspondence to Qianqun Gu or Hyun Park.

Additional information

The authors Xinying Yang, Guojian Zhang, and Xuelian Tang contributed equally to this work.

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Yang, X., Zhang, G., Tang, X. et al. Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect. Mol Cell Biochem 374, 29–36 (2013). https://doi.org/10.1007/s11010-012-1502-9

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  • DOI: https://doi.org/10.1007/s11010-012-1502-9

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