IL-23 in arthritic and inflammatory pain development in mice
IL-23 in arthritic and inflammatory pain development in mice
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DOI：
10.1186/s13075-020-02212-0
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发表时间：
2020-05-29
影响因子：
4.9
通讯作者：
Cook, Andrew D.
中科院分区：
文献类型：
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作者：
Lee, Kevin M. -C.;Zhang, Zihao;Cook, Andrew D.
背景细胞因子白细胞介素-23（IL-23）对炎症性疾病（包括关节炎）的进展至关重要，并且通常与T淋巴细胞生物学相关。我们以前表明，某些淋巴细胞非依赖性，炎性关节炎和疼痛模型有一个类似的要求，肿瘤坏死因子（TNF），粒细胞巨噬细胞集落刺激因子（GM-CSF），和C-C基序配体17（CCL 17）。考虑到细胞因子需求的这种相关性，我们探讨了IL-23是否可能在控制关节炎和炎性疼痛中与这种细胞因子簇相互作用。方法采用小鼠关节炎模型（酵母多糖诱导的关节炎和GM-CSF、TNF和CCL 17驱动的单关节炎）和炎性疼痛模型（足底酵母多糖、GM-CSF、TNF和CCL 17）研究IL-23在疼痛样行为发展中的作用。此外，在存在消炎痛的情况下，在GM-CSF-/-、Tnf（-/-）和Ccl 17（E/E）小鼠中测量了IL-23诱导的炎症性疼痛。疼痛样行为和关节炎分别通过后肢和组织学的相对重量分布进行评估。通过定量PCR分析膝关节和爪皮肤中的细胞因子mRNA表达。通过流式细胞术分析血液和滑膜细胞群。结果我们报道，使用IL-23 p19（-/-）小鼠，先天免疫（酵母聚糖）驱动的关节炎疼痛样行为（本文称为疼痛）完全依赖于IL-23;最佳关节炎疾病发展需要IL-23（P < 0.05）。酵母多糖诱导的炎性疼痛也完全依赖于IL-23。此外，我们发现IL-23 p19（-/-）小鼠中不存在外源性TNF-、GM-CSF-和CCL 17驱动的关节炎疼痛，以及由这些细胞因子中的每一种驱动的炎性疼痛;在这些mBSA引发的模型中，最佳疾病依赖于IL-23（P < 0.05）。支持这种细胞因子联系，相反地发现IL-23（200 ng）可以在4 h诱导炎性疼痛（P < 0.0001），需要每种其他细胞因子以及环氧合酶活性。结论这些发现表明IL-23在先天免疫介导的关节炎和炎性疼痛中的作用与TNF、GM-CSF、CCL 17和类花生酸功能有潜在联系。
Background The cytokine, interleukin-23 (IL-23), can be critical for the progression of inflammatory diseases, including arthritis, and is often associated with T lymphocyte biology. We previously showed that certain lymphocyte-independent, inflammatory arthritis and pain models have a similar requirement for tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF), and C-C motif ligand 17 (CCL17). Given this correlation in cytokine requirements, we explored whether IL-23 might interact with this cytokine cluster in the control of arthritic and inflammatory pain. Methods The role of IL-23 in the development of pain-like behaviour was investigated using mouse arthritis models (zymosan-induced arthritis and GM-CSF-, TNF-, and CCL17-driven monoarticular arthritis) and inflammatory pain models (intraplantar zymosan, GM-CSF, TNF, and CCL17). Additionally, IL-23-induced inflammatory pain was measured inGM-CSF-/-,Tnf(-/-), andCcl17(E/E)mice and in the presence of indomethacin. Pain-like behaviour and arthritis were assessed by relative weight distribution in hindlimbs and histology, respectively. Cytokine mRNA expression in knees and paw skin was analysed by quantitative PCR. Blood and synovial cell populations were analysed by flow cytometry. Results We report, usingIl23p19(-/-)mice, that innate immune (zymosan)-driven arthritic pain-like behaviour (herein referred to as pain) was completely dependent upon IL-23; optimal arthritic disease development required IL-23 (P < 0.05). Zymosan-induced inflammatory pain was also completely dependent on IL-23. In addition, we found that exogenous TNF-, GM-CSF-, and CCL17-driven arthritic pain, as well as inflammatory pain driven by each of these cytokines, were absent inIl23p19(-/-)mice; optimal disease in these mBSA-primed models was dependent on IL-23 (P < 0.05). Supporting this cytokine connection, it was found conversely that IL-23 (200 ng) can induce inflammatory pain at 4 h (P < 0.0001) with a requirement for each of the other cytokines as well as cyclooxygenase activity. Conclusions These findings indicate a role for IL-23 in innate immune-mediated arthritic and inflammatory pain with potential links to TNF, GM-CSF, CCL17, and eicosanoid function.