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重组单体人白细胞介素-22改善小鼠DSS诱导的急性结肠炎

Amelioration of DSS-Induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22.

作者信息

Kim Suhyun, Hong Eun-Hye, Lee Cheol-Ki, Ryu Yiseul, Jeong Hyunjin, Heo Seungnyeong, Lee Joong-Jae, Ko Hyun-Jeong

机构信息

Department of Biochemistry, Kangwon National University, Chuncheon 24341, Korea.

Laboratory of Microbiology and Immunology, Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.

出版信息

Immune Netw. 2022 Mar 30;22(3):e26. doi: 10.4110/in.2022.22.e26. eCollection 2022 Jun.

Abstract

IL-22, a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and non-functional oligomers. Monomeric IL-22 (mIL-22) was highly purified through a series of 3 separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate STAT3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

摘要

白细胞介素-22(IL-22)是一种多效性细胞因子,已知其对受损肠道屏障的再生具有深远影响。IL-22的组织保护特性有望在结肠炎的减轻和治疗中得到潜在应用。然而,由于IL-22在慢性炎症中具有促进疾病的作用,因此需要进行全面评估才能将IL-22应用于临床领域。在此,我们展示了在细菌中有效生产可溶性人IL-22,以证明重组IL-22是否具有改善结肠炎和炎症的能力。IL-22以生物活性单体和无功能寡聚体的形式表达。单体IL-22(mIL-22)通过一系列3种单独的色谱方法和酶促反应进行了高度纯化。我们发现,所得的mIL-22正确折叠,并且能够在HT-29细胞中磷酸化信号转导和转录激活因子3(STAT3)。随后,我们证明mIL-22能够减轻葡聚糖硫酸钠诱导的小鼠急性结肠炎,并抑制促炎细胞因子的产生。总体而言,我们的结果表明,重组mIL-22适合研究内源性IL-22在免疫反应中的生物学作用,并可开发为与炎症性疾病相关的生物制剂。

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