Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

This article was retracted on 05 September 2022

This article has been updated

Abstract

Objective

Tripterine (Trip) is frequently applied to alleviate inflammation in various diseases such as rheumatoid arthritis. Macrophages have both anti-inflammatory and pro-inflammatory functions. However, whether Trip can inhibit cell inflammation in gouty arthritis (GA) remains undiscovered and whether the mechanism involved in macrophage polarization is also undetermined. This paper aims to study the effects of Trip on inflammation and macrophage polarization in GA.

Methods

Monosodium urate (MSU) crystals were used to establish GA mouse models, and bone marrow-derived macrophages (BMDMs) were induced to construct GA cell models. Pretreatments of Trip and injection of Antagomir-449a/Agomir-449a were performed on mice for 6 days. The effects of Trip and miR-449 on toe swelling, joint damage of GA mouse were examined. The alternations on cell morphology, cell proliferation marker Ki67, inflammatory cytokines, NLRP3 inflammasome, and NF-κB signaling-related proteins were also determined both in vivo and in vitro. Dual-luciferase reporter gene assay and RIP assay were adopted to estimate the targeting relationship between miR-449a and NLRP3.

Results

GA mouse model had increased M1 macrophage, intensified inflammation response, along with suppressed miR-449a expression. Following administration of Trip attenuated cell inflammation, promoted macrophage polarize to M2 phenotype, elevated miR-449a expression, repressed the phosphorylation levels of NF-κB signaling-related proteins, and diminished IκBα expression in vivo and in vitro. However, inhibition of miR-449a hindered the favorable effect of Trip on GA and increased NLRP3 inflammasome expression. MiR-449a directly targeted NLRP3. Overexpression of NLRP3 partially eliminated the biological effects of miR-449a agonist.

Conclusion

Trip regulates macrophage polarization through miR-449a/NLRP3 axis and the STAT3/NF-κB pathway to mitigate GA. The elucidation on the molecular mechanism of Trip in GA may provide theoretical guidance for clinical therapy of GA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Change history

References

  1. Cleophas MC, Crisan TO, Joosten LA. Factors modulating the inflammatory response in acute gouty arthritis. Curr Opin Rheumatol. 2017;29:163–70.

    Article  Google Scholar 

  2. Lee HE, Yang G, Kim ND, Jeong S, Jung Y, Choi JY, et al. Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout. Sci Rep. 2016;6:38622.

    Article  CAS  Google Scholar 

  3. Dinesh P, Rasool M. Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats. Int Immunopharmacol. 2017;44:26–37.

    Article  CAS  Google Scholar 

  4. Wang Y, Viollet B, Terkeltaub R, Liu-Bryan R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages. Ann Rheum Dis. 2016;75:286–94.

    Article  CAS  Google Scholar 

  5. Ruiz-Miyazawa KW, Staurengo-Ferrari L, Mizokami SS, Domiciano TP, Vicentini F, Camilios-Neto D, et al. Quercetin inhibits gout arthritis in mice: induction of an opioid-dependent regulation of inflammasome. Inflammopharmacology. 2017;25(5):555–70.

    Article  CAS  Google Scholar 

  6. Vergadi E, Ieronymaki E, Lyroni K, Vaporidi K, Tsatsanis C. Akt signaling pathway in macrophage activation and M1/M2 polarization. J Immunol. 2017;198:1006–14.

    Article  CAS  Google Scholar 

  7. Liu Y, Tang H, Liu X, Chen H, Feng N, Zhang J, et al. Frontline Science: Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviates gouty arthritis. J Leukoc Biol. 2019;105:11–24.

    Article  CAS  Google Scholar 

  8. Mei J, Zhou F, Qiao H, Li H, Tang T. Nerve modulation therapy in gouty arthritis: targeting increased sFRP2 expression in dorsal root ganglion regulates macrophage polarization and alleviates endothelial damage. Theranostics. 2019;9:3707–22.

    Article  CAS  Google Scholar 

  9. Ti D, Hao H, Tong C, Liu J, Dong L, Zheng J, et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J Transl Med. 2015;13:308.

    Article  Google Scholar 

  10. Wang J, Yang Q, Zhang Q, Yin C, Zhou L, Zhou J, et al. Invariant natural killer T cells ameliorate monosodium urate crystal-induced gouty inflammation in mice. Front Immunol. 2017;8:1710.

    Article  Google Scholar 

  11. Venkatesha SH, Dudics S, Astry B, Moudgil KD. Control of autoimmune inflammation by celastrol, a natural triterpenoid. Pathog Dis. 2016;74:ftw059.

    Article  Google Scholar 

  12. Venkatesha SH, Moudgil KD. Celastrol and its role in controlling chronic diseases. Adv Exp Med Biol. 2016;928:267–89.

    Article  CAS  Google Scholar 

  13. Song X, Zhang Y, Dai E, Du H, Wang L. Mechanism of action of celastrol against rheumatoid arthritis: a network pharmacology analysis. Int Immunopharmacol. 2019;74:105725.

    Article  CAS  Google Scholar 

  14. Peng X, Wang J, Li X, Lin L, Xie G, Cui Z, et al. Targeting mast cells and basophils with anti-fcepsilonrialpha fab-conjugated celastrol-loaded micelles suppresses allergic inflammation. J Biomed Nanotechnol. 2015;11:2286–99.

    Article  CAS  Google Scholar 

  15. Li X, Wei W, Zhao Z, Lv S. Tripterine up-regulates miR-223 to alleviate lipopolysaccharide-induced damage in murine chondrogenic ATDC5 cells. Int J Immunopathol Pharmacol. 2019;33:2058738418824521.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Yu Y, Koehn CD, Yue Y, Li S, Thiele GM, Hearth-Holmes MP, et al. Celastrol inhibits inflammatory stimuli-induced neutrophil extracellular trap formation. Curr Mol Med. 2015;15:401–10.

    Article  CAS  Google Scholar 

  17. Luo D, Guo Y, Cheng Y, Zhao J, Wang Y, Rong J. Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-kappaB pathways. Aging (Albany NY). 2017;9:2069–82.

    Article  CAS  Google Scholar 

  18. Jiang L, Hao C, Li Z, Zhang P, Wang S, Yang S, et al. miR-449a induces EndMT, promotes the development of atherosclerosis by targeting the interaction between AdipoR2 and E-cadherin in lipid rafts. Biomed Pharmacother. 2019;109:2293–304.

    Article  CAS  Google Scholar 

  19. Cai Y, Jiang C, Zhu J, Xu K, Ren X, Xu L, et al. miR-449a inhibits cell proliferation, migration, and inflammation by regulating high-mobility group box protein 1 and forms a mutual inhibition loop with Yin Yang 1 in rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Res Ther. 2019;21:134.

    Article  Google Scholar 

  20. Guo C, Fu R, Wang S, Huang Y, Li X, Zhou M, et al. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis. Clin Exp Immunol. 2018;194:231–43.

    Article  CAS  Google Scholar 

  21. Zou Y, Hu W. Investigation of gene expression profiles in a rat adjuvant arthritis model suggests an effective role of triptolide via PI3K-AKT signaling. Exp Ther Med. 2019;17:3999–4006.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang Y, Wei D, Lai Z, Le Y. Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis. Int Immunopharmacol. 2006;6:1825–32.

    Article  CAS  Google Scholar 

  23. Yifan W, Dengming W, Zheng L, Yanping L, Junkan S. Triptolide inhibits CCR5 expressed in synovial tissue of rat adjuvant-induced arthritis. Pharmacol Rep. 2007;59:795–9.

    PubMed  Google Scholar 

  24. Ying W, Cheruku PS, Bazer FW, Safe SH, Zhou B. Investigation of macrophage polarization using bone marrow derived macrophages. J Vis Exp. 2013. https://doi.org/10.3791/50323.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Burja B, Kuret T, Janko T, Topalovic D, Zivkovic L, Mrak-Poljsak K, et al. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med. 2019;6:56.

    Article  CAS  Google Scholar 

  26. Schauer C, Janko C, Munoz LE, Zhao Y, Kienhofer D, Frey B, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20:511–7.

    Article  CAS  Google Scholar 

  27. Pope RM, Tschopp J. The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheum. 2007;56:3183–8.

    Article  CAS  Google Scholar 

  28. Scott O, Roifman CM. NF-kappaB pathway and the Goldilocks principle: Lessons from human disorders of immunity and inflammation. J Allergy Clin Immunol. 2019;143:1688–701.

    Article  Google Scholar 

  29. Ben-David H, Livneh A, Lidar M, Feld O, Haj Yahia S, Grossman C, et al. Toll-like receptor 2 is overexpressed in Familial Mediterranean fever patients and is inhibited by colchicine treatment. Best Pract Res Clin Rheumatol. 2018;32:651–61.

    Article  Google Scholar 

  30. Patel U, Rajasingh S, Samanta S, Cao T, Dawn B, Rajasingh J. Macrophage polarization in response to epigenetic modifiers during infection and inflammation. Drug Discov Today. 2017;22:186–93.

    Article  CAS  Google Scholar 

  31. Kashyap D, Sharma A, Tuli HS, Sak K, Mukherjee T, Bishayee A. Molecular targets of celastrol in cancer: recent trends and advancements. Crit Rev Oncol Hematol. 2018;128:70–81.

    Article  Google Scholar 

  32. Bian M, Du X, Cui J, Wang P, Wang W, Zhu W, et al. Celastrol protects mouse retinas from bright light-induced degeneration through inhibition of oxidative stress and inflammation. J Neuroinflammation. 2016;13:50.

    Article  Google Scholar 

  33. Abu Bakar MH, Sarmidi MR, Tan JS, Mohamad Rosdi MN. Celastrol attenuates mitochondrial dysfunction and inflammation in palmitate-mediated insulin resistance in C3A hepatocytes. Eur J Pharmacol. 2017;799:73–83.

    Article  CAS  Google Scholar 

  34. Lin L, Sun Y, Wang D, Zheng S, Zhang J, Zheng C. Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition. Front Pharmacol. 2015;6:320.

    PubMed  Google Scholar 

  35. Xiong Y, Yan Y, Li Y. Tripterine alleviates LPS-induced inflammatory injury by up-regulation of miR-146a in HaCaT cells. Biomed Pharmacother. 2018;105:798–804.

    Article  CAS  Google Scholar 

  36. Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, et al. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell. 2015;160:62–73.

    Article  CAS  Google Scholar 

  37. Xin W, Wang Q, Zhang D, Wang C. A new mechanism of inhibition of IL-1beta secretion by celastrol through the NLRP3 inflammasome pathway. Eur J Pharmacol. 2017;814:240–7.

    Article  CAS  Google Scholar 

  38. Yu X, Zhao Q, Zhang X, Zhang H, Liu Y, Wu X, et al. Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation. Oncotarget. 2017;8:67300–14.

    Article  Google Scholar 

  39. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018;233:6425–40.

    Article  CAS  Google Scholar 

  40. Fan Y, Mao R, Yang J. NF-kappaB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell. 2013;4:176–85.

    Article  CAS  Google Scholar 

  41. Liu Z, Han Y, Zhao F, Zhao Z, Tian J, Jia K. Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-kappaB pathway. J Cell Biochem. 2019;120:3467–73.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatism Immunology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China

    Yu Wang

Authors
  1. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu Wang.

Ethics declarations

Conflict of interest

The authors declare there is no conflict of interests.

Additional information

Responsible Editor: John Di Battista.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s00011-022-01630-x

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y. RETRACTED ARTICLE: Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis. Inflamm. Res. 70, 323–341 (2021). https://doi.org/10.1007/s00011-021-01439-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-021-01439-0

Keywords

Search

Navigation