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1.
CXC趋化因子配体8(CXC chemokine ligand 8,CXCL8)在结直肠癌等多种肿瘤中高表达,并促进肿瘤恶性进展。研究发现,结直肠癌微环境中有大量M2型巨噬细胞浸润,但CXCL8是否影响M2型巨噬细胞的浸润及其潜在机制尚未可知。本文旨在探讨CXCL8对结直肠癌中M2型巨噬细胞浸润及趋化作用的影响。本研究首先分析了TCGA数据库结直肠癌样本中CXCL8表达水平及免疫细胞浸润情况,并在临床组织中进行验证。随后Western 印迹及qRT-PCR检测5种结直肠癌细胞株CXCL8的表达情况。佛波酯(PMA)及IL-4诱导THP-1至M2型巨噬细胞后,与HCT116、SW480细胞及过表达CXCL8的HCT116(CXCL8/HCT116)、SW480(CXCL8/SW480)共培养,检测M2型巨噬细胞趋化情况。白细胞介素1β(IL-1β)处理HCT116、SW480细胞,检测CXCL8表达情况,与M2型巨噬细胞共培养,分析趋化结果。结果显示,患者癌组织CXCL8表达高于癌旁组织,CXCL8高表达癌组织中存在更多M2型巨噬细胞浸润;IL-1β作用于HCT116或SW480后,CXCL8的mRNA及蛋白质表达水平升高(P<0.05)。Transwell实验证实,CXCL8趋化M2型巨噬细胞(P<0.05)。综上所述,结直肠癌细胞中CXCL8可由IL-1β诱导产生,CXCL8表达增加能够促进M2型巨噬细胞的趋化,结直肠癌微环境中M2型巨噬细胞大量浸润可能与CXCL8表达升高有关。 相似文献
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Wuyang Zhang Zhiwei Dong Dengke Li Bei Li Yuan Liu Xueni Zheng Hui Liu Hongzhi Zhou Kaijin Hu Yang Xue 《Cell proliferation》2021,54(7)
ObjectivesTo clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC).Materials and MethodsTooth extraction models of Ctsk knockout mice (Ctsk ‐/‐) and their wildtype (WT) littermates were used to investigate the effect of CTSK on alveolar bone regeneration. The influences of deletion or inhibition of CTSK by odanacatib (ODN) on proliferation and osteogenic differentiation of JBMMSC were assessed by CCK‐8, Western blot and alizarin red staining. To explore the differently expressed genes, RNA from WT and Ctsk‐/‐ JBMMSC was sent to RNA‐seq. ECAR, glucose consumption and lactate production were measured to identify the effect of Ctsk deficiency or inhibition on glycolysis. At last, we explored whether Ctsk deficiency or inhibition promoted JBMMSC proliferation and osteogenic differentiation through glycolysis.ResultsWe found out that Ctsk knockout could promote alveolar bone regeneration in vivo. In vitro, we confirmed that both Ctsk knockout and inhibition by ODN could promote proliferation of JBMMSC, up‐regulate expression of Runx2 and ALP, and enhance matrix mineralization. RNA‐seq results showed that coding genes of key enzymes in glycolysis were significantly up‐regulated in Ctsk‐/‐ JBMMSC, and Ctsk deficiency or inhibition could promote glycolysis in JBMMSC. After blocking glycolysis by 3PO, the effect of Ctsk deficiency or inhibition on JBMMSC’s regeneration was blocked subsequently.ConclusionsOur findings revealed that Ctsk knockout or inhibition could promote alveolar bone regeneration by enhancing JBMMSC regeneration via glycolysis. These results shed new lights on the regulatory mechanism of CTSK on bone regeneration. 相似文献
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Hanghang Liu Shibo Liu Huanzhong Ji Qiucheng Zhao Yao Liu Pei Hu En Luo 《Cell proliferation》2021,54(6)
ObjectivesAdiponectin signalling has been considered to be a promising target to treat diabetes‐related osteoporosis. However, contradictory results regarding bone formation were observed due to the various isoforms of adiponectin. Therefore, it would be necessary to investigate the effect of adiponectin receptor signals in regulating bone‐fat balance.Materials and MethodsWe primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism‐related cells to investigate the role of Adiponectin receptor signals on bone‐fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration.ResultsWe found that AdipoRon could slightly inhibit the proliferation of pre‐osteoblast and pre‐osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre‐osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre‐osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon‐treated mice showed faster bone regeneration and repressed adipogenesis.ConclusionsOur study demonstrated a pro‐osteogenic, anti‐adipogenic and anti‐osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone‐fat balance regulation. 相似文献
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Ringe J Strassburg S Neumann K Endres M Notter M Burmester GR Kaps C Sittinger M 《Journal of cellular biochemistry》2007,101(1):135-146
The recruitment of bone marrow CD34- mesenchymal stem- and progenitor cells (MSC) and their subsequent differentiation into distinct tissues is the precondition for in situ tissue engineering. The objective of this study was to determine the entire chemokine receptor expression profile of human MSC and to investigate their chemotactic response to the selected chemokines CCL2, CXCL8 and CXCL12. Human MSC were isolated from iliac crest bone marrow aspirates and showed a homogeneous population presenting a typical MSC-related cell surface antigen profile (CD14-, CD34-, CD44+, CD45-, CD166+, SH-2+). The expression profile of all 18 chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that MSC express CC, CXC, C and CX(3)C receptors. Gene expression and immunohistochemical analysis documented that MSC express chemokine receptors CCR2, CCR8, CXCR1, CXCR2 and CXCR3. A dose-dependent chemotactic activity of CXCR4 and CXCR1/CXCR2 ligands CXCL12 and CXCL8 (interleukin-8) was demonstrated using a 96-well chemotaxis assay. In contrast, the CCR2 ligand CCL2 (monocyte chemoattractant protein-1, MCP-1) did not recruited human MSC. In conclusion, we report that the chemokine receptor expression profile of human MSC is much broader than known before. Furthermore, for the first time, we demonstrate that human MSC migrate upon stimulation with CXCL8 but not CCL2. In combination with already known data on MSC recruitment and differentiation these are promising results towards in situ regenerative medicine approaches based on guiding of MSC to sites of degenerated tissues. 相似文献
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Dong H Osmanova V Epstein PM Brocke S 《Biochemical and biophysical research communications》2006,345(2):713-719
The immune system depends on chemokines to recruit lymphocytes to tissues in inflammatory diseases. This study identifies PDE8 as a new target for inhibition of chemotaxis of activated lymphocytes. Chemotactic responses of unstimulated and concanavalin A-stimulated mouse splenocytes and their modulation by agents that stimulate the cAMP signaling pathway were compared. Dibutyryl cAMP inhibited migration of both cell types. In contrast, forskolin and 3-isobutyl-1-methylxanthine each inhibited migration of unstimulated splenocytes, with little effect on migration of stimulated splenocytes. Only dipyridamole alone, a PDE inhibitor capable of inhibiting PDE8, strongly inhibited migration of stimulated and unstimulated splenocytes and this inhibition was enhanced by forskolin and reversed by a PKA antagonist. Following concanavalin A stimulation, mRNA for PDE8A1 was induced. These results suggest that in employing PDE inhibitor therapy for inflammatory illnesses, inhibition of PDE8 may be required to inhibit migration of activated lymphocytes to achieve a full therapeutic effect. 相似文献
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Jinbo Li Xing Li Wen Sun Jiao Zhang Quanquan Yan Jun Wu Jianliang Jin Ruinan Lu Dengshun Miao 《International journal of biological sciences》2022,18(5):2091
Osteoblastic lineage cells (OBCs) are bone-building cells and essential component of hematopoietic niche, but mechanisms whereby bone-building and hematopoiesis-supportive activities of OBCs could be regulated simultaneously remain largely unknown. Here we found that B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) was involved in such a co-regulatory mechanism. In this study, we first found that, accompanied with marked decline of osteogenic activity, the hematopoietic niche in Bmi1 knockout (KO) mice was severely impaired and manifested as CXCL12 expression falls and LSK homing failure; however, intratibial injection with CXCL12 effectively facilitated LSK accumulation in bone marrow of Bmi1 KO mice. To try to rescue these defects in Bmi1 KO mice, we generated Bmi1KO/Sirt1Tg (KO-TG) double mutant mice with Sirt1 specific overexpression in mesenchymal progenitor cells (MPCs) in Bmi1 KO mice, and our data showed that KO-TG mice had significantly increased bone-building activity, elevated Cxcl12 expression by MPCs, increased LSK homing and expanded LSK pool in bone marrow compared to Bmi1 KO mice. Of note, similar improvements in KO-TG mice were observed in Bmi1 KO mice fed with dietary resveratrol, an established Sirt1 activator, comparing with KO control mice. Therefore, pharmacologic activation of Bmi1/Sirt1 signaling pathway could simultaneously promote bone-building and hematopoiesis-supportive activities of OBCs. 相似文献
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目的:探究CXCL1在原发性肝癌中的表达及对人肝癌HepG2细胞增殖的影响。方法:应用免疫组织化学技术(SP二步法)检测48例原发性肝癌组织、13正常肝脏组织中CXCL1表达情况;通过CCK8试剂盒检测CXCL1对HepG2细胞增殖能力的影响。结果:CXCL1在77.1%的原发性肝癌组织中表达,同时CXCL1在原发性肝癌组织中的表达高于正常肝脏组织,差异有统计学意义(P0.01);不同浓度CXCL1处理人肝癌HepG2细胞后,人肝癌HepG2细胞增殖能力明显增强,并且在一定范围内存在明显的剂量效应。结论:CXCL1在原发性肝癌中表达上调;CXCL1能够促进人肝癌HepG2细胞增殖。 相似文献
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研究过表达的趋化因子CXCL12是否通过PI3K/Akt信号途径促进了骨髓基质干细胞膜上缝隙连接蛋白Connexin40、Connexin43和Connexin45的表达。采用重组DNA技术使骨髓基质干细胞过表达趋化因子CXCL12,采用Western blot法测定趋化因子CXCL12过表达后骨髓基质干细胞Connexin40、Connexin43、Connexin45、Akt、pAkt表达的变化情况,并用CXCL12受体和Akt途径阻断剂明确CXCL12和PI3K/Akt途径在这一过程中的作用。基因重组后骨髓干细胞过表达了趋化因子CXCL12,CXCL12过表达使骨髓基质干细胞膜上Connexin40、Connexin43和Connexin45表达明显增多,且CXCL12的这一作用是通过PI3K/Akt这一途径实现的。趋化因子CXCL12通过PI3K/Akt途径使骨髓基质干细胞膜上Connexin40、Connexin43和Connexin45的表达增加,可促进移植后干细胞与宿主心肌细胞形成有效的电耦合,从而有利于移植后干细胞的存活并发挥治疗作用。 相似文献
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《Cell cycle (Georgetown, Tex.)》2013,12(12):2303-2313
Efficient homing of human umbilical cord blood mesenchymal stem cells (hUCBSC) to inflammation sites is crucial for therapeutic use. In glioblastoma multiforme, soluble factors released by the tumor facilitate the migratory capacity of mesenchymal stem cells toward glioma cells. These factors include chemokines and growth inducers. Nonetheless, the mechanistic details of these factors involved in hUCBSC homing have not been clearly delineated. The present study is aimed to deduce specific factors involved in hUCBSC homing by utilizing a glioma stem cell-induced inflammatory lesion model in the mouse brain. Our results show that hUCBSC do not form tumors in athymic nude mice brains and do not elicit immune responses in immunocompetent SKH1 mice. Further, hUCBSC spheroids migrate and invade glioma spheroids, while no effect was observed on rat fetal brain aggregates. Several cytokines, including GRO, MCP-1, IL-8, IL-3, IL-10, Osteopontin and TGF-β2, were constitutively secreted in the naive hUCBSC-conditioned medium, while significant increases of IL-8, GRO, GRO-α, MCP-1 and MCP-2 were observed in glioma stem cell-challenged hUCBSC culture filtrates. Furthermore, hUCBSC showed a stronger migration capacity toward glioma stem cells in vitro and exhibited enhanced migration to glioma stem cells in an intracranial human malignant glioma xenograft model. Our results indicate that multiple cytokines are involved in recruitment of hUCBSC toward glioma stem cells, and that hUCBSC are a potential candidate for glioma therapy. 相似文献
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Wei Xu Ruijun Xu Zhikun Li Yi Wang Ruixi Hu 《Journal of cellular and molecular medicine》2019,23(3):1899-1907
Mesenchymal stem cells (MSCs) have drawn great attention because of their therapeutic potential. It has been suggested that intra‐venous infused MSCs could migrate the site of injury to help repair the damaged tissue. However, the mechanism for MSC migration is still not clear so far. In this study, we reported that hypoxia increased chemotaxis migration of MSCs. At 4 and 6 hours after culturing in hypoxic (1% oxygen) conditions, the number of migrated MSCs was significantly increased. Meanwhile, hypoxia also increased the expression of HIF‐1α and SDF‐1. Using small interference RNA, we knocked down the expression of HIF‐1α in MSCs to study the role of HIF‐1α in hypoxia induced migration. Our data indicated that knocking down the expression of HIF‐1α not only abolished the migration of MSCs, but also reduced the expression of SDF‐1. Combining the results of migration assay and expression at RNA and protein level, we demonstrated a novel mechanism that controls the increase of MSCs migration. This mechanism involved HIF‐1α mediated SDF‐1 expression. These findings provide new insight into the role of HIF‐1α in the hypoxia induced MSC migration and can be a benefit for the development of MSC‐based therapeutics for wound healing. 相似文献
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Kiran Kumar Velpula Venkata Ramesh Dasari Jasti S. Rao 《Cell cycle (Georgetown, Tex.)》2012,11(12):2303-2313
Efficient homing of human umbilical cord blood mesenchymal stem cells (hUCBSC) to inflammation sites is crucial for therapeutic use. In glioblastoma multiforme, soluble factors released by the tumor facilitate the migratory capacity of mesenchymal stem cells toward glioma cells. These factors include chemokines and growth inducers. Nonetheless, the mechanistic details of these factors involved in hUCBSC homing have not been clearly delineated. The present study is aimed to deduce specific factors involved in hUCBSC homing by utilizing a glioma stem cell-induced inflammatory lesion model in the mouse brain. Our results show that hUCBSC do not form tumors in athymic nude mice brains and do not elicit immune responses in immunocompetent SKH1 mice. Further, hUCBSC spheroids migrate and invade glioma spheroids, while no effect was observed on rat fetal brain aggregates. Several cytokines, including GRO, MCP-1, IL-8, IL-3, IL-10, Osteopontin and TGF-β2, were constitutively secreted in the naive hUCBSC-conditioned medium, while significant increases of IL-8, GRO, GRO-α, MCP-1 and MCP-2 were observed in glioma stem cell-challenged hUCBSC culture filtrates. Furthermore, hUCBSC showed a stronger migration capacity toward glioma stem cells in vitro and exhibited enhanced migration to glioma stem cells in an intracranial human malignant glioma xenograft model. Our results indicate that multiple cytokines are involved in recruitment of hUCBSC toward glioma stem cells, and that hUCBSC are a potential candidate for glioma therapy. 相似文献
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Mahmood Rasool Peter Natesan Pushparaj Sajjad Karim 《Saudi Journal of Biological Sciences》2021,28(11):6045-6049
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Dimitrios Agas Giovanna Lacava Maria Giovanna Sabbieti 《Journal of cellular physiology》2019,234(1):192-213
Bone is a multifaceted dynamic tissue, involved in mobility, mineral metabolism, and mesenchymal or stromal and hematopoietic progenitor or stem cells breading. Recently, an endocrine role has been attributed to bone due to its ability to produce at least two hormones (osteocalcin and fibroblast growth factor 23) and to participate directly or indirectly in leptin, insulin, estrogens, and serotonin signaling; regulation; and action. Also, bearing in mind the enormous amounts of substances secreted by the different bone marrow cell types, it becomes understandable the contribution of bone tissue to systemic homeostasis. Besides, bone is a well-known estrogen-responsive tissue, reacting to environmental influences. Thus, it has been coined as a critical target of environmental xenoestrogens, known as endocrine-disrupting chemicals (EDCs). The exposure to EDCs results to disruption or imbalance of the systemic hormonal regulation of the skeleton including bone modeling and remodeling, local hormones, and cytokine or chemokine release. The present report highlights the harmful EDCs effects on bone tissue and provides up-to-date information of xenoestrogen action on proliferation, maturation, and homing of bone marrow inhabitants. 相似文献
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视黄酸对维持正常的雄性睾丸结构和功能起着重要的作用。近来的研究发现,在雄性生殖腺发育过程中有一组基因,它们可以被视黄酸特异性的诱导活化,称为Stra（Stimulated by Retinoic Acid）基因。从鼠源分离得到的Stra8 基因编码一种细胞质蛋白,该基因只特异性的在成熟雄性生殖细胞中表达,其功能被认为与精子形成有关。为研究Stra8 基因的表达特性,我们从小鼠的基因组中克隆了Stra8 基因的启动子序列（1.4kb）。将Stra8 基因的1.4kb启动子序列克隆到pEGFP-1载体的EGFP基因之前,构建成由Stra8 基因1.4kb启动子序列调控表达绿色荧光蛋白的pStra8-EGFP载体。将其分别转化到不同类型的细胞中,如小鼠ES-129细胞、人胎儿胰腺干细胞、小鼠骨髓间充质干细胞和小鼠精原干细胞等,通过荧光显微镜观察发现,绿色荧光蛋白只在小鼠精原干细胞中表达,表明Stra8基因是组织特异性表达的基因。将pStra8-EGFP转化小鼠骨髓间充质干细胞,经G418筛选2周后,用视黄酸诱导,12h培养后,有一部分转化pStra8-EGFP载体的细胞表达绿色荧光蛋白。RT-PCR证明这些细胞中有精原干细胞特异表达基因Stra8 的转录,还有生殖细胞特异表达基因CyclinA8 和Oct4的转录,这些结果说明小鼠骨髓间充质细胞经视黄酸的诱导可以向生殖细胞方向分化。 相似文献