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Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway

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Abstract

Objective

The prevalence of allergic rhinitis is high, making it a relatively common chronic condition. Countless patients suffer from seasonal Allergic rhinitis (AR). The objective of this investigation is to examine the potential involvement of common pollen allergens in seasonal allergic rhinitis, and study the proposed mechanism of Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the induction of AR.

Method

A mouse AR model (sensitized group) was constructed with pollen extracts and ovalbumin (OVA) of Artemisia annua (An), Artemisia argyi (Ar) and Artemisia Sieversiana (Si), and thereafter, AR symptom score was performed. After successful modeling, mouse serum and nasal mucosa tissues were extracted for subsequent experiments. The expression levels of immunoglobulin E (IgE), Interleukin (IL)-4, IL-5, IL-13 and Tumor Necrosis Factor-α (TNF-α) in serum were detected using Enzyme-linked immunosorbent assay (ELISA); Hematoxylin–eosin (H&E) staining methods were used to observe the pathological changes of the nasal mucosal tissue; Utilizing immunohistochemistry (IHC) staining, the expression levels of TLR4, MyD88 and Nuclear factor kappa B (NF-κB) p65 in mouse nasal mucosa were quantified; The mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of sensitized mice were detected with Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Finally, the in vitro culture of Human nasal mucosal epithelial cells (HNEpC) cells was conducted, and cells were treated with 200 µg/ml Artemisia annua pollen extract and OVA for 24 h. Western Blot assay was used to detect the expression level of TLR4, MyD88 and NF-κB p65 proteins before and after HNEpC cells were treated with MyD88 inhibitor ST-2825.

Result

On the second day after AR stimulation, the mice showed obvious AR symptoms. H&E results showed that compared to the control group, the nasal mucosal tissue in the sensitized group was significantly more inflamed. Furthermore, ELISA assay showed increased expression levels of IgE, IL-4, IL-5, IL-13 and TNF-α in serum of mice induced by OVA and Artemisia annua pollen, Artemisia argyi pollen and Artemisia Sieversiana pollen than those of the control group. However, the expression level of IL-2 was lower than that of the control group (P < 0.05). Using Immunohistochemistry staining visually observed the expression levels of TLR4, MyD88 and NF-κB p65 in mouse nasal mucosa tissues and quantitatively analyzed. The expression levels of TLR4, MyD88 and NF-κB p65 in the sensitized group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The results from qRT-PCR and Western Blot showed that the mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of the sensitized group were significantly higher than those in the control group (P < 0.05). Finally, HNEpC cells were cultured in vitro and analyzed using Western Blot. The expression levels of TLR4, MyD88 and NF-κB p65 in OVA and An groups were significantly increased (P < 0.05). After ST-2825 treatment, TLR4 protein expression was significantly increased (P < 0.05) and MyD88 and NF-κB p65 protein expression were significantly decreased (P < 0.05).

Conclusion

To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

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Data availability

The data of the present study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank 51runse (www.51runse.com) for the English editing during the preparation of this manuscript.

Funding

This work was supported by the Research Project Supported by Shanxi Scholarship Council of China (2022–194);The First Hospital of Shanxi Medical University special fund research project, 136 special projects(Y2021136031);The First Hospital of Shanxi Medical University special fund research project, 136 special projects(Y2022136020).

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Author notes

  1. Jing Zhang and Lu Gao have contributed equally to this work.

Authors and Affiliations

  1. Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Jing Zhang, Lu Gao, Dongdong Yu, Yulan Song, Yan Zhao & Yan Feng

  2. Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Jing Zhang & Lu Gao

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  1. Jing Zhang
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  2. Lu Gao
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  4. Yulan Song
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  5. Yan Zhao
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Contributions

ZJ: designed the research and wrote the draft; GL: analyzed the experiment data; YDD and SYL: recorded animal behavior and provided data; FY: provided resources and supervised the entire work.

Corresponding author

Correspondence to Yan Feng.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Review Committee of experimental animal welfare in the first hospital of Shanxi Medical University (No:DWLL-2024–001). All methods were performed in accordance with the relevant guidelines and regulations.

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Zhang, J., Gao, L., Yu, D. et al. Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway. Mol Biol Rep 51, 319 (2024). https://doi.org/10.1007/s11033-024-09350-7

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