Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Biology, College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.
Int J Mol Sci. 2022 Jan 11;23(2):757. doi: 10.3390/ijms23020757.
Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.
白细胞介素 (IL)-22 是炎症反应的有力介质。IL-22 受体由 IL-22Rα 和 IL-10Rβ 亚基组成。先前的研究表明，IL-22Rα 的表达局限于皮肤、胰腺、肠道、肝脏、肺和肾脏中的非造血细胞。虽然 IL-22 参与了炎症反应的发展，但尚未有其在大脑炎症中作用的报道。在这里，我们使用 RT-PCR、Western blot、流式细胞术、免疫组织化学和微阵列分析，使用小胶质细胞系、海马神经元细胞系和炎症小鼠脑组织，研究了 IL-22 和 IL-22Rα 在大脑中的作用。用重组 IL-22 处理 BV2 和 HT22 细胞会增加促炎细胞因子 IL-6 和 TNF-α 以及环氧化酶 (COX)-2 和前列腺素 E2 的表达水平。我们还发现 JNK 和 STAT3 信号通路在 IL-22 介导的炎症介质增加中起重要作用。微阵列分析显示，IL-22 处理的 HT22 细胞中炎症相关基因的表达上调。最后，我们发现 IL-22Rα 在大脑中自发表达，并在炎症小鼠大脑中上调。总体而言，我们的结果表明，IL-22 与 IL-22Rα 的相互作用在大脑炎症反应的发展中起作用。
