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Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation

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Abstract

Inflammation contributes to the pathogenesis of lupus nephritis (LN), which is the most serious complication that increases mortality of systemic lupus erythematosus (SLE). Sophocarpine is a type of quinolizidine alkaloid that possesses anti-inflammatory property. This study investigated the speculation that sophocarpine might play a beneficial effect in LN. Female MRL/lpr mice received sophocarpine treatment for 8 weeks. Renal function and histopathology were evaluated. The level of immune complex deposition was measured by immunofluorescent staining, and the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and anti-double-stranded DNA (anti-dsDNA) antibodies were measured by ELISA. Western blotting was carried out to evaluate the levels of proteins involved in NLRP3 inflammasome and NF-κB pathway. Sophocarpine treatment reduced urine protein excretion, blood urea nitrogen, and attenuated renal tissue damage. The levels of renal immune complex deposition, serum anti-dsDNA, and serum and renal inflammatory cytokines were significantly reduced by sophocarpine. Sophocarpine treatment reduced the levels of proteins that form NLRP3 inflammasome. Activation of NF-κB in the kidney was inhibited by sophocarpine. Sophocarpine could ameliorate experimental LN in MRL/lpr. These effects might be through suppressing NLRP3 inflammasome and NF-κB pathway.

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References

  1. Schwartz N, Goilav B, Putterman C. The pathogenesis, diagnosis and treatment of lupus nephritis. Curr Opin Rheumatol. 2014;26:502–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Lech M, Anders H-J. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013;24:1357–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Yung S, Cheung KF, Zhang Q, Chan TM. Mediators of inflammation and their effect on resident renal cells: implications in lupus nephritis. Clin Dev Immunol 2013;2013:317682, 1, 10.

  4. Kuroiwa T, Lee EG. Cellular interactions in the pathogenesis of lupus nephritis: the role of T cells and macrophages in the amplification of the inflammatory process in the kidney. Lupus. 1998;7:597–603.

    Article  PubMed  CAS  Google Scholar 

  5. Nowling TK, Gilkeson GS. Mechanisms of tissue injury in lupus nephritis. Arthritis Res Ther. 2011;13:250.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kamen DL, Zollars ES. Corticosteroids in lupus nephritis and central nervous system lupus. Rheum Dis Clin N Am. 2016;42:63–73.

    Article  Google Scholar 

  7. Lin Z, Huang CF, Liu XS, Jiang J. In vitro anti-tumour activities of quinolizidine alkaloids derived from Sophora flavescens Ait. Basic Clin Pharmacol Toxicol. 2011;108:304–9.

    Article  PubMed  CAS  Google Scholar 

  8. Gao Y, Li G, Li C, Zhu X, Li M, Fu C, et al. Anti-nociceptive and anti-inflammatory activity of sophocarpine. J Ethnopharmacol 2009;125:324–329.

  9. Zhang Y, Wang S, Li Y, Xiao Z, Hu Z, Zhang J. Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice. Int Immunopharmacol. 2008;8:1767–72.

    Article  PubMed  CAS  Google Scholar 

  10. Gao Y, Jiang W, Dong C, Li C, Fu X, Min L, et al. Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways. Toxicol in Vitro 2012;26:1–6.

  11. Muraoka M, Hasegawa H, Kohno M, Inoue A, Miyazaki T, Terada M, et al. IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice. Arthritis Rheum 2006;54:3591–3600.

  12. Perry D, Sang A, Yin Y, Zheng YY, Morel L. Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011;2011:271694, 1, 19.

  13. Yuan Y, Liu Z. Isoflurane attenuates murine lupus nephritis by inhibiting NLRP3 inflammasome activation. Int J Clin Exp Med. 2015;8:17730–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Zhao J, Zhang H, Huang Y, Wang H, Wang S, Zhao C, et al. Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation. Int Immunopharmacol 2013;17:116–122.

  15. Zhao J, Wang H, Dai C, Wang H, Zhang H, Huang Y, et al. P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the NLRP3/ASC/caspase 1 pathway. Arthritis Rheum 2013;65:3176–3185.

  16. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10:417–26.

    Article  PubMed  CAS  Google Scholar 

  17. Alcocer-Gómez E, Castejón-Vega B, Cordero MD. Chapter six - stress-induced NLRP3 Inflammasome in human diseases. In: Donev R, editor. Advances in protein chemistry and structural biology. Academic Press; 2017. p. 127–62.

  18. Shin MS, Kang Y, Lee N, Wahl ER, Kim SH, Kang KS, et al. Self double-stranded (ds)DNA induces IL-1β production from human monocytes by activating NLRP3 Inflammasome in the presence of anti–dsDNA antibodies. J Immunol. 2013;190:1407–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Kahlenberg JM, Kaplan MJ. The inflammasome and lupus- another innate immune mechanism contributing to disease pathogenesis? Curr Opin Rheumatol. 2014;26:475–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kahlenberg JM, Carmona-Rivera C, Smith CK, Kaplan MJ. Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages. J Immunol. 2013;190:1217–26.

    Article  PubMed  CAS  Google Scholar 

  21. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 Inflammasome activation by regulating NLRP3 expression. J Immunol 2009;183:787–791.

  22. Blackwell TS, Christman JW. The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol. 1997;17:3–9.

    Article  PubMed  CAS  Google Scholar 

  23. Kawai T, Akira S. Signaling to NF-κB by toll-like receptors. Trends Mol Med. 2007;13:460–9.

    Article  PubMed  CAS  Google Scholar 

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Funding

This research was supported by a grant from the fund of National Science Foundation of China (81700585).

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Correspondence to Mengjun Wang.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Li, X., Wang, M., Hong, H. et al. Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation. Immunol Res 66, 521–527 (2018). https://doi.org/10.1007/s12026-018-9012-9

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  • DOI: https://doi.org/10.1007/s12026-018-9012-9

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