炎症环境下白细胞介素1β增强间充质干细胞的迁移及黏附能力

Interleukin-1beta enhances migration and adhesion of mesenchymal stem cells in inflammatory environments

背景:间充质干细胞具有更新迅速、定向归巢、组织修复和免疫调节等特性,因此,有治疗炎症性疾病的潜能。在炎症情况下,白细胞介素1β高表达,外源性输入或生物体内的间充质干细胞不可避免地生存在高浓度白细胞介素1β的环境中。目的:研究在炎症环境下白细胞介素1β与间充质干细胞的相互作用及其影响间充质干细胞迁移和黏附能力的机制,为调整干细胞治疗策略提供理论基础。方法:由第一作者应用计算机在中国知网、万方、维普、PubMed、Web of Science数据库检索涉及白细胞介素1β增强间充质干细胞迁移和黏附能力的相关文献,中文数据库检索词为“白细胞介素1β,间充质干细胞,核转录因子κB,MAPK,ERK,p38,迁移,黏附”;英文数据库检索词为“IL-1β,mesenchymal stem cells,MSC,NF-κB,MAPK,ERK,p38,migration,adhesion”,最终纳入65篇进行综述分析。结果与结论:①在炎症环境中,白细胞介素1β可调节间充质干细胞的迁移和黏附能力,该效应可能通过白细胞介素1RI募集IRAK1,并依次激活TAK1与IKK,IKK磷酸化后,激活核转录因子κB和ERK信号通路,或通过p38通路上调CXCR的表达,促进间充质干细胞的迁移和黏附。但未来仍需要在此基础上围绕间充质干细胞的遗传背景、白细胞介素1β的剂量和处理时间展开进一步标准化研究。②在体外实验中使用白细胞介素1β预刺激间充质干细胞,一方面可以改变间充质干细胞的生存环境,调节分泌因子,从而促使其向更具抗炎功能方向发展;另一方面,在产生更高水平的抗炎和促营养因子的前提下,抽提的间充质干细胞外泌体可以发挥抗炎作用。③目前在各类动物疾病模型研究中已证实,白细胞介素1β预刺激调节间充质干细胞免疫调节能力,从而影响炎症的发展转归,但限于只是临床前的基础研究,白细胞介素1β预处理间充质干细胞的干细胞治疗效果及安全性需要在临床领域进一步验证。

BACKGROUND:Mesenchymal stem cells possess characteristics such as rapid renewal,targeted homing,tissue repair,and immune regulation,which provide potential for the treatment of inflammatory diseases.In most inflammatory diseases,interleukin-1βis highly expressed.Both exogenous and endogenous mesenchymal stem cells unavoidably exist in an environment with high interleukin-1βconcentration.OBJECTIVE:To study the interaction of interleukin-1βwith mesenchymal stem cells in inflammatory environment and the mechanism of its influence on the migration and adhesion of mesenchymal stem cells to provide a theoretical basis for adjusting stem cell therapy strategies.METHODS:The first author searched for studies involving interleukin-1βenhancing migration and adhesion of mesenchymal stem cells by computer on CNKI,WanFang,VIP,PubMed,and Web of Science using search terms“interleukin-1β,mesenchymal stem cell,nuclear factor-κB,MAPK,ERK,p38,migration,adhesion”in Chinese and English.The literature tracing method was also used to search for some of the literature.Finally,65 articles were included in the review analysis.RESULTS AND CONCLUSION:(1)In the inflammatory environment,interleukin-1βcan regulate the migration and adhesion ability of mesenchymal stem cells.This effect may be achieved by recruiting IRAK1 through interleukin-1RI and then activating TAK1 and IKK in turn.After IKK phosphorylation,nuclear factor-κB and ERK signaling pathways are activated or CXCR expression is upregulated through the p38 pathway to promote mesenchymal stem cell migration and adhesion.However,further standardized research needs to be carried out based on the genetic background of mesenchymal stem cells,the dose and processing time of interleukin-1β.(2)In vitro experiments using pre-stimulated mesenchymal stem cells with interleukin-1βcan change the survival environment of mesenchymal stem cells and alter their secretion factors to make them develop towards a more anti-inflammatory direction.On the other hand,under the premise of producing higher levels of anti-inflammatory and pro-nutrient factors,extracted mesenchymal stem cell exosomes can exert anti-inflammatory effects.(3)It has been observed in various animal disease models that pre-stimulating mesenchymal stem cells with interleukin-1βregulates their immune regulation ability,thereby affecting the development and outcome of inflammation.However,this is limited to preclinical basic research only;further verification on efficacy and safety of stem cell therapy with interleukin-1βpre-treated mesenchymal stem cells is required in clinical settings.