白細(xì)胞介素22（IL-22）是一個相對發(fā)現(xiàn)較晚的細(xì)胞因子，目前已被發(fā)現(xiàn)能誘導(dǎo)人角質(zhì)形成細(xì)胞和成纖維樣滑膜細(xì)胞（FLS）的增殖,，從而導(dǎo)致自身免疫性疾病的發(fā)生如牛皮癬,、類風(fēng)濕關(guān)節(jié)炎（RA）等,。這些疾病的特點(diǎn)就是會角質(zhì)細(xì)胞和滑膜增生。
PI3K/Akt/mTOR信號級聯(lián)在細(xì)胞生長和存活中起著至關(guān)重要的作用,。因此,，一項(xiàng)最新研究考察白細(xì)胞介素22是否是通過調(diào)控PI3K/Akt/mTOR信息信號級聯(lián)誘導(dǎo)角質(zhì)形成細(xì)胞和滑膜增生。
科研人員從接受了整容手術(shù)健康志愿者的皮膚和銀屑病關(guān)節(jié)炎（PSA）患者以及RA患者滑膜組織中分離出表皮角質(zhì)形成細(xì)胞（NHEK）和FLS用于開展研究。MTT法檢測了IL-22對NHEK和FLS的增殖作用,。
印跡檢測磷Akt/mTOR的酸化,，并進(jìn)一步通過實(shí)時聚合酶鏈反應(yīng)（RT-PCR）檢測確認(rèn)了上述蛋白mRNA水平的變化。我們觀察到IL-22能誘導(dǎo)NHEK和FLS 中Akt和mTOR的磷酸化,，而IL-22誘導(dǎo)磷酸化效應(yīng)能被雷帕霉素和NVP-BEZ235所抑制,。雷帕霉素和NVP-BEZ235是PI3K/mTOR抑制劑。
此外,，RT-PCR實(shí)驗(yàn)發(fā)現(xiàn)在NHEK中,，IL-22顯著上調(diào)AKT1和mTOR的基因表達(dá)。這些結(jié)果表明IL-22誘導(dǎo)NHEK和FLS的增殖是依賴于PI3K/Akt/mTOR信號通路的,。這項(xiàng)最新研究有助制定針對自身免疫性疾病如牛皮癬,、類風(fēng)濕關(guān)節(jié)炎的靶向PI3K/Akt/mTOR的新療法。（生物谷：Bioon.com）
編譯自：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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PMID:
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.
