白细胞介素22（IL-22）是一个相对发现较晚的细胞因子，目前已被发现能诱导人角质形成细胞和成纤维样滑膜细胞（FLS）的增殖，从而导致自身免疫性疾病的发生如牛皮癣、类风湿关节炎（RA）等。这些疾病的特点就是会角质细胞和滑膜增生。
PI3K/Akt/mTOR信号级联在细胞生长和存活中起着至关重要的作用。因此，一项最新研究考察白细胞介素22是否是通过调控PI3K/Akt/mTOR信息信号级联诱导角质形成细胞和滑膜增生。
科研人员从接受了整容手术健康志愿者的皮肤和银屑病关节炎（PSA）患者以及RA患者滑膜组织中分离出表皮角质形成细胞（NHEK）和FLS用于开展研究。MTT法检测了IL-22对NHEK和FLS的增殖作用。
印迹检测磷Akt/mTOR的酸化，并进一步通过实时聚合酶链反应（RT-PCR）检测确认了上述蛋白mRNA水平的变化。我们观察到IL-22能诱导NHEK和FLS 中Akt和mTOR的磷酸化，而IL-22诱导磷酸化效应能被雷帕霉素和NVP-BEZ235所抑制。雷帕霉素和NVP-BEZ235是PI3K/mTOR抑制剂。
此外，RT-PCR实验发现在NHEK中，IL-22显著上调AKT1和mTOR的基因表达。这些结果表明IL-22诱导NHEK和FLS的增殖是依赖于PI3K/Akt/mTOR信号通路的。这项最新研究有助制定针对自身免疫性疾病如牛皮癣、类风湿关节炎的靶向PI3K/Akt/mTOR的新疗法。（生物谷：Bioon.com）
编译自：IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade
doi:10.1016/j.cyto.2012.06.316
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IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade
Anupam Mitraa,Smriti Kundu Raychaudhurib,Siba P. Raychaudhurib
Interleukin 22 (IL-22), a relatively new cytokine has been found to induce significant proliferation of human keratinocytes and fibroblast like synoviocytes (FLS) and thus plays an important role in the pathogenesis of autoimmune diseases like psoriasis and rheumatoid arthritis (RA) which are characterized by hyperproliferation of keratinocytes and FLS respectively. PI3K/Akt/mTOR signaling cascade plays crucial role in cell growth and survival. Therefore our objective was to see the regulatory role of PI3K/Akt/mTOR signaling cascade in IL-22 induced proliferation of keratinocytes and FLS. Normal human epidermal keratinocytes (NHEK) and FLS were isolated from skin of healthy volunteer’s undergone plastic surgery and synovial tissue of psoriatic arthritis (PsA) and RA patients respectively. IL-22 induced proliferation of NHEK and FLS was measured by MTT assay. Phosphorylation of Akt/mTOR was determined by western blot assay and further confirmed by real time polymerase chain reaction (RT-PCR). We observed that IL-22 induced significant proliferation of NHEK and FLS which was effectively inhibited by dual kinase (PI3K/mTOR) inhibitor, NVP-BEZ235 and specific mTOR inhibitor, Rapamycin. In NHEK and FLS, IL-22 significantly induced phosphorylation of Akt and mTOR which was effectively blocked by Rapamycin and NVP-BEZ235. Further we did RT-PCR in NHEK and found that IL-22 significantly upregulated AKT1 and MTOR gene. These results show that IL-22 induced proliferation of NHEK and FLS is dependent on PI3K/Akt/mTOR signaling pathway. This novel observation provides the scope to develop new therapeutics targeting PI3K/Akt/mTOR signaling pathway in autoimmune diseases like psoriasis and rheumatoid arthritis. Rapamycin and NVP-BEZ235 significantly inhibited IL-22 induced cell proliferation. IL-22 increased phosphorylation of Akt and mTOR in keratinocytes and synoviocytes. IL-22 upregulated AKT1 and MTOR gene in keratinocytes. IL-22 induced cell proliferation is mediated by Akt/mTOR signaling pathway.
