Quercetin inhibits the activity and function of dendritic cells through the TLR4/IRAK4/NF-κB signaling pathway

Chenglin Kang; Xiaomei Li; Peng Liu; Yue Liu; Yuan Niu; Xianhai Zeng; Jiangqi Liu; Hailiang Zhao; Shuqi Qiu

doi:10.5114/wo.2023.133741

eISSN: 1897-4309
ISSN: 1428-2526

Contemporary Oncology/Współczesna Onkologia

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3/2023
vol. 27

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abstract:

Original paper

Quercetin inhibits the activity and function of dendritic cells through the TLR4/IRAK4/NF-κB signaling pathway

Chenglin Kang

^{1, 2, 3}

,

Xiaomei Li

³

,

Peng Liu

^{1, 2}

,

Yue Liu

^{1, 2}

,

Yuan Niu

⁴

,

Xianhai Zeng

^{1, 2}

,

Jiangqi Liu

^{1, 2}

,

Hailiang Zhao

^{1, 2}

,

Shuqi Qiu

^{1, 2}

Department of Graduate and Scientific Research, Zunyi Medical University Zhuhai Campus, Zhuhai, People’s Republic of China
Department of Otolaryngology, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Shenzhen, People’s Republic of China
Department of Otolaryngology, Second People’s Hospital of Gansu Province, Lanzhou, People’s Republic of China
Department of Neurology, Second People’s Hospital of Gansu Province, Lanzhou, People’s Republic of China

Contemp Oncol (Pozn) 2023; 27 (3): 182–189

DOI: https://doi.org/10.5114/wo.2023.133741

Online publish date: 2023/12/21

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Introduction:
To investigate the inhibitory effect of quercetin (QUE) on dendritic cells (DCs) through the toll-like receptor 4/interleukin-1 receptor-associated kinase 4/nuclear factor kappa-B (TLR4/IRAK4/NF-κB) signalling pathway.

Material and methods:
CCK-8 and apoptosis assays were performed to determine the optimal concentration and action time of QUE to inhibit DCs. Protein extracts from treated DCs were used for Western blotting experiments to determine the relative expression levels of TLR4, IRAK4, and NF-κB p65 proteins. Changes in the ratio of CD86 and CD11c positive cells on the DCs surface were detected using flow cytometry. The molecular docking technique was used to analyse the binding site and free energy of QUE and IRAK4.

Results:
CCK-8 and apoptosis assays suggested that QUE inhibited the activity and function of DCs in a time-dose-dependent manner. The results of Western blotting suggested that the relative expression levels of TLR4, IRAK4, and NF-κB p65 proteins were increased in the lipopolysaccharide (LPS) group compared with the normal control group, and the relative expression of the above proteins was decreased after treatment with QUE and IRAK4-IN-4. The results of flow cytometry suggested that LPS increased the expression of CD86 and CD11c on the surface of DCs, and QUE and IRAK4-IN-4 decreased the expression of CD86 and CD11c induced by LPS. Molecular docking results showed that the binding sites of QUE and IRAK4 were stable, with the minimum binding energies comparable to that of IRAK4-IN-4.

Conclusions:
Quercetin may inhibit the activity and function of DCs through the TLR4/IRAK4/NF-κB signalling pathway, and IRAK4 may be its target.

keywords:

Quercetin inhibits the activity and function of dendritic cells through the TLR4/IRAK4/NF-κB signaling pathway

Chenglin Kang 1, 2, 3 , Xiaomei Li 3 , Peng Liu 1, 2 , Yue Liu 1, 2 , Yuan Niu 4 , Xianhai Zeng 1, 2 , Jiangqi Liu 1, 2 , Hailiang Zhao 1, 2 , Shuqi Qiu 1, 2

quercetin, dendritic cells, TLR4/IRAK4/NF--κB signalling pathway

Chenglin Kang

^{1, 2, 3}

,

Xiaomei Li

³

,

Peng Liu

^{1, 2}

,

Yue Liu

^{1, 2}

,

Yuan Niu

⁴

,

Xianhai Zeng

^{1, 2}

,

Jiangqi Liu

^{1, 2}

,

Hailiang Zhao

^{1, 2}

,

Shuqi Qiu

^{1, 2}