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Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells

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Abstract

Background

Mesangial proinflammatory chemokine/cytokine expressions via innate immunity play a pivotal role in the pathogenesis of glomerulonephritis. CXCL1/GROα is a strong neutrophil chemoattractant cytokine and reportedly plays an important role in regional inflammatory reactions. However, detailed signaling of mesangial CXCL1 expression induced by viral or “pseudoviral” immunity remains to be determined.

Methods

We treated normal human mesangial cells (MCs) in culture with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of CXCL1 by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR and enzyme-linked immunosorbent assay. To elucidate the poly IC-induced signaling pathway for CXCL1 expression, we subjected the cells to RNA interference against Toll-like receptor (TLR) 3, retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), interferon (IFN)-β, nuclear factor (NF)-κB p65 and IFN regulatory factor (IRF) 3. We also conducted an immunofluorescence study to examine mesangial CXCL1 expression in biopsy specimens from patients with lupus nephritis (LN) and IgA nephropathy (IgAN).

Results

We found that activation of TLR3 signaling could induce the expression of CXCL1 in MCs. NF-κB, IRF3 and IFN-β, but neither RIG-I nor MDA5, were found to be involved in mesangial CXCL1 expression in this setting. Induction of CXCL1 by poly IC was inhibited by pretreatment of cells with dexamethasone. Intense glomerular CXCL1 expression was observed in biopsy specimens from patients with LN, whereas only a trace staining occurred in specimens from patients with IgAN.

Conclusion

TLR3 signaling also contributes to the CXCL1 expression in MCs. These observations further support the implication of viral and “pseudoviral” immunity in the pathogenesis of inflammatory renal diseases, especially in 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., M. S. and H. T.), and by Grant for Hirosaki University Institutional Research (T. I. and T. M.). The authors thank A. Yamamoto, K. Nakata, A. Ono and K. Munakata for assistance.

Conflict of interest

None to be declared.

Author information

Authors and Affiliations

  1. Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Tadaatsu Imaizumi, Chihiro Segawa, Tomoh Matsumiya & Hidemi Yoshida

  2. Department of Pediatrics, Hirosaki University Hospital, 53 Hon-cho, Hirosaki, 036-8563, Japan

    Tomomi Aizawa, Kazushi Tsuruga & Hiroshi Tanaka

  3. Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Michiko Shimada

  4. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Shogo Kawaguchi

  5. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan

    Kensuke Joh

  6. Department of School Health Science, Faculty of Education, Hirosaki University, 1 Bunkyo-cho, Hirosaki, 036-8560, Japan

    Hiroshi Tanaka

Authors
  1. Tadaatsu Imaizumi
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  2. Tomomi Aizawa
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  3. Chihiro Segawa
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  7. Tomoh Matsumiya
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  8. Hidemi Yoshida
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  9. Kensuke Joh
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  10. Hiroshi Tanaka
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Corresponding author

Correspondence to Hiroshi Tanaka.

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Imaizumi, T., Aizawa, T., Segawa, C. et al. Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells. Clin Exp Nephrol 19, 761–770 (2015). https://doi.org/10.1007/s10157-014-1060-4

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  • DOI: https://doi.org/10.1007/s10157-014-1060-4

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