Erythroleukemia Cell Secretion and Erythroid Cell Differentiation-Inhibiting Factors
Velibor Krsmanović, James F. Whitfield in Malignant Cell Secretion, 2019
A polypeptide factor called differentiation-inhibiting activity (DIA) has been detected in the medium conditioned by Buffalo rat liver cells, which suppresses the differentiation of embryonic stem (ES) cells in vitro and maintains them in culture with stem cell morphology and biochemical phenotype.177-179 DIA is also able to support the growth of DA-la MoMulv-induced leukemia cells and is related to a human factor referred to as HILDA (human interleukin for DA cells).180,181 Moreover, the sequence of cDNA encoding HILDA181 is identical to that reported for human LIF.173 On the other hand, it has been observed that recombinant LIF has ES differentiation-inhibiting activity.182 It is of interest to mention that a leukemia-inhibitory factor, such as LIF, which suppresses the proliferation of murine Ml myeloid leukemia cells by inducing their differentiation,172-174 can also serve as a growth factor for another murine interleukin-3-dependent leukemia cell line.180 This shows that the growth-promoting and differentiation-inducing capabilities depend on the target cell type, as shown for erythropoietin which is required for proliferation, survival, and differentiation of CFU-E erythroid progenitors,25,26 but the lymphoblastic cell line DA-1 is also shown to be responsive to erythropoietin for survival and growth.27
Regulation of the α2-Macroglobulin Gene
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
In gel retardation assays with Hep G2 extracts, the APRF band showed the same mobility as when rat liver nuclear extracts were used (Figure 11). To study whether human APRF also has binding specificity identical to the factor from rat liver, we used the same labeled oligonucleotides in a gel retardation assay as in the experiments discussed above for rat liver nuclear extracts. As observed for rat APRF, the human factor binds cooperatively to two binding sites in the rat α2-M APRE and also binds the C-site of the rat α1-acid glycoprotein gene (Figure 12). Leukemia inhibitory factor has been shown to induce in hepatocytes the same set of acute phase proteins as IL-6.49 To study whether this effect is due to an activation of the same transcription factor, we performed a gel retardation assay with nuclear extracts from Hep G2 cells treated for 15 min with leukemia inhibitory factor. As shown in Figure 13, leukemia inhibitory factor rapidly induced a factor bindingto the rat α2-M core site. The complex formed by this factor has the same mobility in native gels as APRF, indicating that it is probably identical or very similar to APRF. Thus, the signal transduction pathways of IL-6 and leukemia inhibitory factor may converge to activate APRF.
Current developments in human stem cell research and clinical translation
Christine Hauskeller, Arne Manzeschke, Anja Pichl in The Matrix of Stem Cell Research, 2019
iPSCs must be extensively characterized for pluripotency on the morphological, molecular, and functional levels. Morphology and growth characteristics are amongst the earliest selection criteria for iPSCs. Like hESCs, human iPSCs grow in tight but flat colonies with a distinct outer border and pronounced individual cell borders (Maherali and Hochedlinger, 2008; Asprer and Lakshmipathy, 2015). Each cell has an epithelial cobblestone-like morphology and prominent nucleoli. In contrast, mouse iPS and ES cell colonies are dome shaped with a ‘shiny’ border. Under appropriate culture conditions, stably pluripotent iPSC clones grow indefinitely as they have an extensive self-renewal potential. Frequently, human iPSCs are cultured on MEF with specific culture media. Today, MEF-free culture systems are available using fully synthetic culture media, which are particularly important for clinical purposes. Irrespectively of the culture system, human iPSCs rely on basic fibroblast growth factor (bFGF) signalling to maintain pluripotency. In contrast, mouse iPSCs and ES cells rely on the leukaemia inhibitory factor (LIF) to maintain pluripotency (Maherali and Hochedlinger, 2008).
Leukemia Inhibitory Factor Impairs the Function of Peripheral γδT Cells in Patients with Colorectal Cancer
Published in Immunological Investigations, 2023
Xueyan Xi, Ting Deng, Fen Qiu, Yunhe Zhu, Yumei Li, Gang Li, Yang Guo, Boyu Du
As a member of the IL-6 cytokine family, leukemia inhibitory factor (LIF) is highly expressed in cancer tissues, and its serum level is increased in several solid tumor diseases (Bian et al. 2021; Nicola and Babon 2015; Shi et al. 2019; Viswanadhapalli et al. 2021; Yu et al. 2014). The effects of LIF are mainly exerted by the combination of LIF and its receptor complex, which is composed of two subunits: LIF receptor (LIFR) and gp130. LIFR determines the specificity of the receptor complex (Nicola and Babon 2015; Viswanadhapalli et al. 2021). Recent studies have revealed that LIF contributes to the progression of certain cancers, and its expression is correlated with poor prognosis in various cancer diseases (Pascual-Garcia et al. 2019; Shi et al. 2019; Viswanadhapalli et al. 2021). LIF can facilitate the formation of an immunosuppressive tumor microenvironment via the regulation of tumor-associated macrophage generation in ovarian cancer (Duluc et al. 2007). LIF has also been observed to regulate protumoral cytokine expression in tumor-associated macrophages and CD8+ T cell tumor infiltration (Pascual-Garcia et al. 2019). As a result, LIF is considered a promising drug target, and its blocking antibody (MSC-1) is currently being evaluated in clinical trials (ClinicalTrials.gov Identifier: NCT03490669). However, whether LIF regulates the cytotoxic function of peripheral γδT cells is not fully known.
Leukemia inhibitory factor (LIF) modulates the development of dendritic cells in a dual manner
Published in Immunopharmacology and Immunotoxicology, 2019
Atefeh Yaftiyan, Maryam Eskandarian, Amir Hossein Jahangiri, Nazanin Atieh Kazemi Sefat, Seyed Mohammad Moazzeni
Leukemia inhibitory factor (LIF) is a highly glycosylated pleiotropic member of interleukin-6 (IL-6) cytokine family, which primarily acts upon binding to LIF receptor (LIFR) and gp130 (IL-6 family shared receptor subunit) heterodimer [10]. Functional LIFRs are detected on a number of different cells including myeloid cells, T lymphocytes, DCs, and hepatocytes [11,12]. Many studies have reported that LIF is involved in a broad and diverse range of actions in endocrine, neural, hepatic, stromal, muscular, and renal systems [13]. Independently of these capabilities, substantial stack of evidence suggests that the cytokine is directly linked to several immunological events [11,14,15]. It appears that LIF is a key stimulator for the generation and progression of tumors, and increased serum levels of LIF does seem to correlate with tumor recurrence and metastasis [16,17].
Effect of single-dose depot leuprolide acetate on embryonal implantation: an experimental rat model
Published in Gynecological Endocrinology, 2020
Mustafa Emre Ercin, Gokhan Erdil
Embryonal implantation is an intricate, yet unknown, process in which numerous cellular, hormonal, and molecular factors are involved in the apposition, adhesion, and invasion stages [1]. Mucin-1 (MUC-1) is an increasing glycoprotein on the luminal epithelial surface in the endometrium in the receptive phase and acts as a physical barrier between the endometrial cell surface and external environment [2]. Glycodelin A is one of the most frequently secreted glycoproteins from the secretory and decidualized endometrium and has a crucial role in facilitating the implantation process and maintaining the pregnancy because of its immunosuppressive properties [3]. Leukemia inhibitory factor (LIF) is involved in a variety of processes, including receptivity of endometrium, decidualization, blastocyst growth and development, embryo-endometrial interaction, trophoblast invasion, and immune-modulation, which plays a significant role in embryo implantation [4].
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