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Neferine Attenuates HDM-Induced Allergic Inflammation by Inhibiting the Activation of Dendritic Cell

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Abstract

House dust mite (HDM) acts as an environmental antigen that might cause chronic allergic diseases. Neferine (NEF) shows anti-inflammation therapeutic effects. This study is to explore the protection role of NEF against HDM-induced allergic inflammation. HDM-induced allergic asthmatic C57BL/6J mice models were established. Differential histological staining was used to analyze lung tissue pathological scores. Flow cytometry was used to analyze subtypes and biomarker expression of immune cells. RT-PCR and ELISA were used to test cytokines-related gene and/or protein expression levels. Western blot was performed to investigate the signaling pathway that mediates allergic inflammation from mice lung tissue and bone marrow–derived dendritic cells (BMDCs). H&E and PAS staining results indicate NEF significantly attenuated inflammatory index and the percentage of goblet cells in the lung tissue induced by HDM. The HDM-elevated TH2 and TH17 cells were significantly decreased by NEF; inflammatory cytokines Il-4, Il-13 and Il-17 were dramatically downregulated in the NEF plus HDM group compared with HDM alone. CD40+ and CD86+ DCs, eosinophils and mast cells, and ILC2 cells were decreased by NEF which was elevated under HDM stimulation. In vivo and ex vivo investigations indicated NEF can attenuate the activated NF-κB signaling induced by HDM is involved in allergic inflammatory immune response and regulates cytokines-related gene expression. HDM-activated DCs promoted differentiation of TH2 and TH17 cells but were attenuated by NEF. This study suggests NEF interrupts the overexpression of some cytokines released by DCs, TH2, and TH17 cells; NEF attenuates HDM-induced allergic inflammation via inhibiting NF-κB signaling of DCs.

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Availability of Data and Materials

The data that support this study are available from the corresponding authors upon reasonable request.

Abbreviations

APCs:

Antigen-presenting cells

CD:

Cluster of differentiation

DC:

Dendritic cell

HDM:

House dust mite

IgE:

Immunoglobulin E

IL:

Interleukin

ILC2:

Group 2 innate lymphoid cells

i.p.:

Intraperitoneal injection

i.n.:

Intranasal

NEF:

Neferine

NF-κB:

Nuclear factor-kappa B

MHC-II:

Major histocompatibility complex class II

MLN:

Mediastinal lymph node

OX40L:

Ligand for OX40 or CD134

TH:

T helper cell

TNF-α:

Tumor necrosis factor α

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Funding

This work was supported by the National Natural Science Foundation of China (no. 81900028 to Yun Zhang, no. 82100021 to Hongmei Tang), the Natural Science Foundation of Sichuan Province (no. 2022NSFSC1306 to Yun Zhang), the Foundation of Luzhou Science and Technology Program and Southwest Medical University (no. 2020LZXNYDJ24 to **ng Wang, no. 2021LZXNYD-J19 to Yun Zhang), and the Sichuan Science and Technology Program (no. 2022YFS0629 to Gang Qin).

Author information

Author notes

  1. Linlin Guo

    Present address: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, USA

  2. Qiao Wang and Linlin Guo contributed equally to this work.

Authors and Affiliations

  1. Inflammation and Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Qiao Wang, Ziling Zeng, Hongmei Tang, Hang Hu, **efang Yuan, **ng Wang & Yun Zhang

  2. Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Qiao Wang, Ziling Zeng, Hang Hu, Jun Deng & Yun Zhang

  3. Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH, USA

    Linlin Guo

  4. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University, Nan**g, 210009, China

    Yueru Huang

  5. Department of Otolaryngology Head and Neck Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Gang Qin

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Contributions

X.W., Y.Z., and L.L.G conceived and designed the research. L.L.G and X.W. drafted the manuscript. W.Q., Z.L.Z., Y.R.H., H.M.T., H.H., X.F.Y., J.D., G.Q., and X.W. performed the experiments. W.Q., Y.Z., and X.W. analyzed the data. L.L.G and X.W. edited the article. All authors read and approved the final version of the article. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Linlin Guo, **ng Wang or Yun Zhang.

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All animal experiments (including euthanasia) were in compliance with the regulations and guidelines of the Southwest Medical University Institutional Animal Care Committee (approval no. 201903-117) and were conducted according to the AAALAC and IACUC guidelines.

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Wang, Q., Guo, L., Zeng, Z. et al. Neferine Attenuates HDM-Induced Allergic Inflammation by Inhibiting the Activation of Dendritic Cell. Inflammation 46, 2433–2448 (2023). https://doi.org/10.1007/s10753-023-01891-6

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