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Interleukin 6: Role in the Pathogenesis of Cancer
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
The gene for IL-6 has been cloned and sequenced, and its structure described [17]. It is a 15- to 30-kDa glycoprotein, consisting of 212 amino acids, based on a sequence deduced from cloned IL-6 copy deoxyribonucleic acid (cDNA) [4–7,17]. It is differentially modified by glycosylation, resulting in the range of molecular weights seen for this cytokine. The gene for IL-6 in humans is on chromosome 7; it consists of 5 exons and 4 introns, with the same exon/intron pattern as the gene for granulocyte colony-stimulating factor (G-CSF) [4–7], There is some amino acid sequence similarity between IL-6 and G-CSF, suggesting that there may be some similarity in the tertiary structure of these molecules. Also, IL-6 appears to be related to various other defined cytokines, including oncostatin M (OsM), interleukin 11 (IL-11), ciliary neurotrophic growth factor (CNTF), and leukemia inhibitory factor (LIF) [7,18]. Therefore, IL-6, along with various other cytokines, appears to belong to a family of related IL-6-like cytokines [6,7].
Blood transfusion in patients requiring long-term support
Published in Jennifer Duguid, Lawrence Tim Goodnough, Michael J. Desmond, Transfusion Medicine in Practice, 2020
A breakthrough in the pharmacological management of chronic thrombocytopenia due to bone marrow failure is still awaited. Preliminary results with low-dose interleukin-11 (IL-11) showed a response in platelet counts in 38% of patients with bone marrow failure (AA and MDS).29 Currently there are no published studies of thrombopoietin in this setting.
Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Anthony J. Demetris, J.G. Lunz, Vladimir Subbotin, Tong Wu, Isao Nozaki, Sarah Contrucci, Xia Yin
Since many biliary tract diseases and ductular reactions are accompanied by peribiliary inflammation and BEC proliferation, our laboratory has been actively investigating the effects of various cytokines on BEC biology and pathophysiology.50 This has led to the observation that exogenous recombinant IL-6 can stimulate growth of primary human BEC cultures kept in serum-free medium.46,50 IL-6 is a member of a family of cytokines that includes interleukin 11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (GNTF), and cardiotrophin-1 (CT-1). All of these so-called “IL-6-type” cytokines share a common signal-transducing transmembrane receptor, gp130, which plays an important role in the regulation of complex cellular processes such as gene activation, proliferation, and differentiation.71 Insulin-like growth factor-I and platelet derived growth factor BB were also able to weakly stimulate human BEC proliferation, in vitro.50 Insulin-like growth factor-I also stimulate rat BEC growth.72 Other inflammatory mediators tested in our laboratory on human BEC, such as interleukin-4, (gamma)-interferon, phytohemagglutinin, and platelet-derived growth factors AA and AB do not increase BEC DNA synthesis, in vitro.50
Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11
Published in Immunological Investigations, 2023
Wenjing Ye, Qian Wang, Li Zhao, Changcheng Wang, Dandan Zhang, Mengyu Zhou, Fangfang Chen, Weiguo Wang, Zaihua Zhu, Wenyu Guo, Yun Liu, Hejian Zou, Yu Xue
Interleukin −11 (IL−11) has been recently reported to be a profibrotic cytokine that is elevated in patients with SSc (Adami et al. 2021; Cook and Schafer 2020). RNA sequencing studies have shown that the IL−11 gene was significantly upregulated in skin fibroblasts from SSc patients and lung fibroblasts from patients with SSc-associated lung interstitial disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF), compared to healthy controls (Denton et al. 2018; Lindahl et al. 2013). Animal experiments have revealed that the injection of recombinant mouse IL−11 (rmIL−11) leads to heart and renal fibrosis in mice, accompanied by organ dysfunction (Schafer et al. 2017). Other studies have demonstrated that either knock out of il−11ra1 or pharmacological inhibition of IL−11 could attenuate pulmonary fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse models (Ng et al. 2019, 2020). These data indicate that IL−11 promotes fibrosis through its classical pathway, in which IL−11 binds to its cell membrane receptor IL−11 Rα.
The safety and efficacy of interleukin 11 for radiation injury
Published in Expert Opinion on Drug Safety, 2023
Interleukin 11 (IL-11) is a member of the IL-6 family with several, well-documented modes of biological action, namely and most notably, stimulatory and maturational actions on megakaryocytopoiesis within hematopoietic tissues and related thrombocytopoiesis, along with anti-inflammatory and cytoprotective effects on both gastrointestinal (GI) crypts and hematopoietic progenitors [1]. IL-11 belongs to the gp130 family of cytokines and besides IL-6, IL-11 is the only member of this family which acts on a homodimer of the ubiquitously expressed gp130 co-receptor. Responsiveness of cells is, therefore, determined by the presence of the IL-11 receptor (the IL-6 receptor in the case of IL-6). It might be possible that certain cells are not responsive to IL-11 due to the lack of the IL-11 receptor expression. In such a case, the use of a ‘Hyper-IL-11’ (soluble IL-11 receptor-α fused with IL-11 without any artificial linker to avoid induction of antibody production) might be not only possible but perhaps appropriate [2].
MEK/ERK/RUNX2 Pathway-Mediated IL-11 Autocrine Promotes the Activation of Müller Glial Cells during Diabetic Retinopathy
Published in Current Eye Research, 2022
Na Ji, Yang Guo, Songbai Liu, Manhui Zhu, Yuanyuan Tu, Jiahui Du, Xiaoxiao Wang, Ying Wang, E. Song
Circular RNA-ZRANB1 (cZRANB1) acts as a miRNA sponge to regulate the functions of MGCs through cZRANB1/microRNA-217 (miR-217)/Runt-related transcription factor 2 (RUNX2) network,8 indicating that RUNX2 is located in MGCs. As a transcript factor, RUNX2 regulates the transcription of multiple target genes, including Interleukin-11 (IL-11).9 IL-11, the number of interleukin-6 (IL-6) cytokine family, is secreted by MGCs10 that constitutively express the receptor of IL-11, which is named as interleukin 11 receptor subunit alpha (IL-11RA).11 IL-11 promotes the activation of primary human fibroblasts in response to transforming growth factor β1 (TGFβ1) exposure.12 Therefore, we speculated that IL-11 binding to IL-11RA on MGCs could form an autocrine loop to facilitate Müller glial cell (MGC) activation.