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Tumor necrosis factor-α synergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells: possible involvement in the pathogenesis of lupus nephritis

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Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Aim

It has been reported that tumor necrosis factor (TNF)-α plays dual controversial roles, beneficial or detrimental, in the pathogenesis of murine lupus nephritis (LN). However, its precise role in the development of human LN remains to be determined.

Methods

We examine the effect of pretreatment with TNF-α on the toll-like receptor 3 (TLR3) signaling induced by polyinosinic-polycytidylic acid (poly IC), a synthetic analog of viral dsRNA that makes “pseudoviral” infection in cultured normal human mesangial cells, and analyzed the expression of CC chemokine ligand 5 (CCL5) via TLR3/interferon (IFN)-β/retinoic acid-inducible gene-I (RIG-I) pathway by reverse transcriptase-polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay.

Results

We found synergistic effect of TNF-α, even at low level, on the expression of CCL5 induced by poly IC in a concentration-dependent manner, in comparison with that by poly IC alone. Knockdown of either IFN-β or RIG-I decreased CCL5 expression induced by TNF-α followed by poly IC.

Conclusion

Pretreatment with TNF-α leads marked activation of the TLR3/IFN-β/RIG-I/CCL5 axis induced by “pseudoviral” infection. Since chronic local activation of proinflammatory cytokines including TNF-α in resident renal cells may exist in patients with active lupus, synergistic effect of TNF-α and “pseudoviral” infection is possibly involved in the development of LN.

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Acknowledgments

This work was supported by grants-in-aid for Science from the Ministry of Education, Culture, Sports, Science and Technology of Japan (T. I. and H. T.), and by Grant for Hirosaki University Institutional Research (T. I.) and a Priority Research Grant for Young Scientists Designated by the President of Hirosaki University (T. M.). The authors thank A. Yamamoto, K. Nakata, A. Ono and K. Munakata for assistance.

Conflict of interest

No conflict of interest to declare.

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Authors and Affiliations

  1. Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan

    Tadaatsu Imaizumi, Ryo Hayakari, Fei Xing, Pengfei Meng, Tomoh Matsumiya, Hidemi Yoshida & Liang Wang

  2. Department of Pediatrics, Hirosaki University Hospital, Hirosaki, 036-8563, Japan

    Tomomi Aizawa, Kazushi Tsuruga & Hiroshi Tanaka

  3. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki University, Hirosaki, 036-8562, Japan

    Tetsuya Tatsuta

  4. Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki, 036-8560, Japan

    Hiroshi Tanaka

Authors
  1. Tadaatsu Imaizumi
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  2. Tomomi Aizawa
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  3. Ryo Hayakari
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  4. Fei Xing
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  6. Kazushi Tsuruga
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  7. Tomoh Matsumiya
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  8. Hidemi Yoshida
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  9. Liang Wang
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  10. Tetsuya Tatsuta
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  11. Hiroshi Tanaka
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Corresponding author

Correspondence to Hiroshi Tanaka.

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Imaizumi, T., Aizawa, T., Hayakari, R. et al. Tumor necrosis factor-α synergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells: possible involvement in the pathogenesis of lupus nephritis. Clin Exp Nephrol 19, 75–81 (2015). https://doi.org/10.1007/s10157-014-0956-3

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  • DOI: https://doi.org/10.1007/s10157-014-0956-3

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