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Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages

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Abstract

Supervillin (SVIL) is an actin-binding and membrane-associated protein, which belongs to villin/gelsolin family. It has been reported that SVIL was involved in the regulation of macrophages’ movement and lipopolysaccharide (LPS) increased the SVIL mRNA expression in neutrophils, but the underlying mechanisms remain unknown. This work investigated the underlying molecular mechanisms of LPS regulating SVIL expression in macrophages and hence the possible role of SVIL in LPS-induced inflammation. We found that in THP-1-derived macrophages, LPS obviously increased SVIL mRNA and protein expression. Inhibition of TLR4 by Resatorvid (Res) remarkably reversed the LPS-induced SVIL expression. Additionally, inhibition of ERK1/2 signaling pathway (by U0126 or GDC-0994) and NF-κB (by BAY) significantly reduced the LPS-induced SVIL expression. Interestingly, down-regulation of SVIL by SVIL-specific shRNAs significantly attenuated the expression of IL-6, IL-1β & TNF-α induced by LPS at both mRNA and protein levels. Furthermore, we also observed that SVIL knockdown decreased the proportion of cells in G2/M phase and increased the proportion of cells in S & G0-1 phase of THP-1 derived macrophages, but did not influence the cell viability. Taken together, we demonstrated that LPS induced the expression of SVIL via activating TLR4/NF-κB and ERK1/2 MAPK pathways, and SVIL participated in the inflammatory response of LPS-induced IL-6, IL-1β and TNF-α upregulation in macrophages.

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AVAILABILITY OF DATA AND MATERIALS

The materials and analyzed data sets generated during the current study are available from the corresponding author on reasonable request.

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ACKNOWLEDGEMENTS

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Funding

This work was supported by National Natural Science Foundation of China (No. 81773724 & 81573424 and No. 81803520).

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Authors and Affiliations

  1. Department of Pharmacology, Nanjing Medical University, Longmian Dadao 101, Nanjing, 211166, China

    Jun Zhou, Yuhui Que, Lihua Pan, Xu Li, Chao Zhu, Lai Jin & Shengnan Li

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  1. Jun Zhou
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  2. Yuhui Que
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  3. Lihua Pan
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  4. Xu Li
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Contributions

Shengnan Li and Jun Zhou designed the study, and drafted the manuscript. Jun Zhou, Yuhui Que, Lihua Pan and Xu Li performed the experiments and analyzed the data. Lai Jin contributed essential reagents and revised the manuscript. Chao Zhu revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lai Jin or Shengnan Li.

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Zhou, J., Que, Y., Pan, L. et al. Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages. Inflammation 45, 356–371 (2022). https://doi.org/10.1007/s10753-021-01551-7

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