scholarly journals The Enigmatic Cytokine Oncostatin M and Roles in Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Carl D. Richards
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Cell Proliferation ◽  
Chronic Inflammation ◽  
Inflammatory Disease ◽  
Oncostatin M ◽  
Therapeutic Approaches ◽  
Pleiotropic Functions

Oncostatin M is a secreted cytokine involved in homeostasis and in diseases involving chronic inflammation. It is a member of the gp130 family of cytokines that have pleiotropic functions in differentiation, cell proliferation, and hematopoetic, immunologic, and inflammatory networks. However, Oncostatin M also has activities novel to mediators of this cytokine family and others and may have fundamental roles in mechanisms of inflammation in pathology. Studies have explored Oncostatin M functions in cancer, bone metabolism, liver regeneration, and conditions with chronic inflammation including rheumatoid arthritis, lung and skin inflammatory disease, atherosclerosis, and cardiovascular disease. This paper will review Oncostatin M biology in a historical fashion and focus on its unique activities, in vitro and in vivo, that differentiate it from other cytokines and inspire further study or consideration in therapeutic approaches.

scholarly journals IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
James W. Swann ◽  
Lada A. Koneva ◽  
Daniel Regan-Komito ◽  
Stephen N. Sansom ◽  
Fiona Powrie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Chronic Inflammation ◽  
Inflammatory Disease ◽  
Erythropoietin Receptor ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

An important comorbidity of chronic inflammation is anemia, which may be related to dysregulated activity of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Among HSPCs, we found that the receptor for IL-33, ST2, is expressed preferentially and highly on erythroid progenitors. Induction of inflammatory spondyloarthritis in mice increased IL-33 in BM plasma, and IL-33 was required for inflammation-dependent suppression of erythropoiesis in BM. Conversely, administration of IL-33 in healthy mice suppressed erythropoiesis, decreased hemoglobin expression, and caused anemia. Using purified erythroid progenitors in vitro, we show that IL-33 directly inhibited terminal maturation. This effect was dependent on NF-κB activation and associated with altered signaling events downstream of the erythropoietin receptor. Accordingly, IL-33 also suppressed erythropoietin-accelerated erythropoiesis in vivo. These results reveal a role for IL-33 in pathogenesis of anemia during inflammatory disease and define a new target for its treatment.

scholarly journals PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ning Zhang ◽  
Chi-Wen Lo ◽  
Takeshi Utsunomiya ◽  
Masahiro Maruyama ◽  
Ejun Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Chronic Inflammation ◽  
Lentiviral Vector ◽  
Great Promise ◽  
Anti Inflammatory ◽  
Potential Strategy

Abstract Background Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect. Methods In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis. Results PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone. Conclusions Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.

scholarly journals WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Ba ◽  
Ying Huang ◽  
Pan Shen ◽  
Yao Huang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Promising Alternative

Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported.Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy.Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments.Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway.Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway.

Modified LDL Immune Complexes and Cardiovascular Disease

2019 ◽  
Vol 26 (9) ◽  
pp. 1680-1692 ◽  
Author(s):  
Maria F. Lopes-Virella ◽  
Gabriel Virella
Keyword(s):  
Cardiovascular Disease ◽  
Cell Proliferation ◽  
Immune Complexes ◽  
Oxidized Ldl ◽  
Atheromatous Plaque ◽  
Vascular Events ◽  
Fibrous Cap ◽  
Macrophage Apoptosis

Modified forms of LDL, both spontaneously formed in the organism or prepared in the laboratory, are immunogenic. As a consequence, antigen-antibody complexes (immune complexes, IC) formed in vivo can be measured in the peripheral blood, and their levels are strong predictors of cardiovascular disease (CVD). It has been possible to generate antibodies that recognize different LDL modifications, allowing the analysis of circulating IC constitution. Clinical studies showed that the antigenic constitution of the IC has a modulating effect on the development of CVD. Patients whose IC react strongly with antibodies to copper oxidized LDL (oxLDL) show progressive development of atherosclerosis as demonstrated by increased intima–media thickness and increased coronary calcification scores. In contrast, patients whose IC react strongly with antibodies to the heavily oxidized malondialdehyde LDL prepared in vitro (MDA-LDL) are at a high risk of acute vascular events, mainly myocardial infarction. In vitro studies have shown that while oxLDL IC induce both cell proliferation and mild to moderate macrophage apoptosis, MDA-LDL IC induce a more marked macrophage apoptosis but not cell proliferation. In addition, MDA-LDL IC induce the release of higher levels of matrix metalloproteinases and TNF than oxLDL IC. High levels of TNF are likely to be a major factor leading to apoptosis and high levels of metalloproteinases are likely to play a role in the thinning of the fibrous cap of the atheromatous plaque. The combination of apoptosis and fibrous cap thinning is a well-known characteristic of vulnerable plaques, which are more prone to rupture and responsible for the majority of acute cardiovascular events.

scholarly journals Chronic Inflammation-Induced Senescence Impairs Immunomodulatory Properties of Synovial Fluid Mesenchymal Stem Cells in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Hyeon-Jeong Lee ◽  
Won-Jae Lee ◽  
Sun-Chul Hwang ◽  
Yong-Ho Choi ◽  
Saetbyul Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Chronic Inflammation ◽  
Cellular Senescence ◽  
Average Duration ◽  
Duration Of Disease

Abstract BackgroundAlthough immunomodulation properties of mesenchymal stem cells (MSCs) has been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the alteration of disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. MethodsWe established the MSCs derived from synovial fluid (SF) from age-matched early (average duration of disease: 1.7 years) and long-standing (average duration of disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then comparatively analyzed the characteristics of MSCs such as stemness, proliferation, cellular senescence, in vitro differentiation and in vivo immunomodulation properties.ResultsThe presence of MSC populations in the SF from RA patients was identified and we found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulation properties and attenuation of anti-arthritic capacity in an RA animal model than E-SF-MSCs. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuation of immunomodulation properties at similar levels to that of L-SF-MSCs in an RA joint mimicking milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to long-term exposure to the chronic inflammation milieu, the progression of cellular senescence, attenuation of immunomodulation properties and loss of anti-arthritic potentials are more often identified in SF-MSCs of long-standing RA than early RA. ConclusionWe conclude that a chronic RA inflammation milieu affected the potential of MSCs; therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.

scholarly journals Bone marrow–derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6461-6464 ◽  
Author(s):  
Akm Khyrul Wara ◽  
Kevin Croce ◽  
ShiYin Foo ◽  
Xinghui Sun ◽  
Basak Icli ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Bone Marrow ◽  
Functional Ability ◽  
Hindlimb Ischemia ◽  
Therapeutic Approaches ◽  
Hematopoietic Stem ◽  
Heterogeneous Nature ◽  
Novel Therapeutic

Abstract Clinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

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