scholarly journals Oncostatin M Mediates Adipocyte Expression and Secretion of Stromal-Derived Factor 1

Biology ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 19
Author(s):  
Hardy Hang ◽  
Jennifer Bailey ◽  
Carrie Elks
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Target Genes ◽  
Immune Cell ◽  
Tissue Homeostasis ◽  
Oncostatin M ◽  
Cytokines And Chemokines ◽  
Gene And Protein Expression ◽  
Cell Balance

Adipose tissue homeostasis depends on interactions between stromal cells, adipocytes, and the cytokines and chemokines they produce. The gp130 cytokine, oncostatin M (OSM), plays a role in adipose tissue homeostasis. Mice, lacking the OSM receptor (OSMR) in adipocytes (OsmrFKO mice), exhibit derangements in adipose tissue, insulin sensitivity, and immune cell balance. Here, we describe a possible role for the chemokine stromal-derived factor 1 (SDF-1) in these alterations. We treated 3T3-L1 adipocytes with OSM and observed a suppression of SDF-1 gene expression and protein secretion, an effect which was partially blunted by OSMR knockdown. However, OsmrFKO mice also exhibited decreased SDF-1 gene and protein expression in adipose tissue. These contrasting results suggest that the loss of adipocyte OSM–OSMR signaling in vivo may be indirectly affecting adipokine production and secretion by altering OSM target genes to ultimately decrease SDF-1 expression in the OsmrFKO mouse. We conclude that adipocyte OSM–OSMR signaling plays a role in adipose tissue SDF-1 production and may mitigate its effects on adipose tissue homeostasis.

scholarly journals Cdx2 regulates immune cell infiltration in the intestine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simon Chewchuk ◽  
Sanzida Jahan ◽  
David Lohnes
Keyword(s):  
Intestinal Epithelium ◽  
Target Genes ◽  
Immune Cell ◽  
Cell Number ◽  
Macrophage Infiltration ◽  
Intestinal Homeostasis ◽  
Chronic Inflammatory Response ◽  
Complex Protein ◽  
Inflammatory Phenotype

AbstractThe intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes, macrophages and dendritic cells. These cells serve a number of roles including mitigation of infection and to stimulate regeneration in response to damage. The transcription factor Cdx2, and to a lesser extent Cdx1, plays essential roles in intestinal homeostasis, and acts as a context-dependent tumour suppressor in colorectal cancer. Deletion of Cdx2 from the murine intestinal epithelium leads to macrophage infiltration resulting in a chronic inflammatory response. However the mechanisms by which Cdx2 loss evokes this response are poorly understood. To better understand this relationship, we used a conditional mouse model lacking all intestinal Cdx function to identify potential target genes which may contribute to this inflammatory phenotype. One such candidate encodes the histocompatability complex protein H2-T3, which functions to regulate intestinal iCD8α lymphocyte activity. We found that Cdx2 occupies the H3-T3 promoter in vivo and directly regulates its expression via a Cdx response element. Loss of Cdx function leads to a rapid and pronounced attenuation of H2-T3, followed by a decrease in iCD8α cell number, an increase in macrophage infiltration and activation of pro-inflammatory cascades. These findings suggest a previously unrecognized role for Cdx in intestinal homeostasis through H2-T3-dependent regulation of iCD8α cells.

scholarly journals Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1401 ◽  
Author(s):  
Marta Magatti ◽  
Francesca Romana Stefani ◽  
Andrea Papait ◽  
Anna Cargnoni ◽  
Alice Masserdotti ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Immune Cell Subsets ◽  
New Perspective ◽  
Antigen Presenting ◽  
Open Question ◽  
Maternal Tolerance

During pregnancy, a successful coexistence between the mother and the semi-allogenic fetus occurs which requires a dynamic immune system to guarantee an efficient immune protection against possible infections and tolerance toward fetal antigens. The mechanism of fetal-maternal tolerance is still an open question. There is growing in vitro and in vivo evidence that mesenchymal stromal cells (MSC) which are present in perinatal tissues have a prominent role in generating a functional microenvironment critical to a successful pregnancy. This review highlights the immunomodulatory properties of perinatal MSC and their impact on the major immune cell subsets present in the uterus during pregnancy, such as natural killer cells, antigen-presenting cells (macrophages and dendritic cells), and T cells. Here, we discuss the current understanding and the possible contribution of perinatal MSC in the establishment of fetal-maternal tolerance, providing a new perspective on the physiology of gestation.

P2572Human iPSC-derived cardiomyocytes preserve murine heart function after myocardial infarction unlike adipose tissue-derived stromal cells

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Dulak ◽  
J Stepniewski ◽  
M Tomczyk ◽  
K Andrysiak ◽  
I Kraszewska ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Luciferase Activity ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Rational Approach ◽  
Acute Mi ◽  
In Vivo Administration

Abstract Introduction Despite progress in pharmacological treatment of myocardial infarction (MI), there is still an immense need for novel therapies for this life-threatening condition. Accordingly, cell-based therapies have been extensively investigated with most studies focusing on mesenchymal stromal cells. However due to their inability to differentiate into cardiomyocytes as well as limited survival upon in vivo administration, no effective treatment of MI has been developed. In contrast, application of hiPSC-derived cardiomyocytes (hiPSC-CM) represent biologically rational approach with pre-clinical studies confirming their therapeutic potential in various models of MI. However further optimization is required due to limited survival of hiPSC-CM upon in vivo administration. Therefore, we evaluated the therapeutic potential of genetically modified hiPSC-CM in murine model of acute MI and compared it to the effect of adipose tissue-derived stromal cells (ADSC). Methods In the first step hiPSC overexpressing GFP, luciferase (Luc) and pro-angiogenic and cardioprotective factors: heme oxygenase-1 (HO-1, heme degrading enzyme) or stromal cell-derived factor-1 (SDF-1, pro-angiogenic chemokine) were subjected to cardiac differentiation which yielded in each group 70–90% cardiac troponin T-positive contracting cells. hiPSC-CM (5x105 in 10 μl) were administered into NOD-SCID mice which underwent permanent ligation of left anterior descending (LAD) coronary artery. The cells were injected into the peri-infarct zone. Mice subjected to sham operation as well as injected with saline after MI were used as controls. The ultrasonography of hearts was performed on day 7, 14, 28 and 42 whereas the presence of hiPSC-CM was monitored using IVIS Spectrum system upon administration of luciferin and analysed in sections of collected hearts. The same experimental scheme was used to assess therapeutic potential of ADSC (CD105+CD73+CD90+CD44+CD146-CD34-) overexpressing luciferase and GFP. Results Ultrasonography demonstrated that upon delivery of hiPSC-CM the left ventricle ejection fraction (LVEF) was very significantly higher in comparison to control group injected with saline after induction of MI. In contrast, no improvement of LVEF was observed after administration of ADSC. Interestingly, measurements of luciferase activity revealed the strongest bioluminescent signal in the hearts of mice transplanted with iPSC-CM-HO1 42 days after MI. Importantly, the survival of hiPSC-CM in murine myocardium six weeks upon administration was further confirmed with immunofluorescent analysis of heart sections using human specific anti-Ku80 antibody. Again, luciferase activity was not observed upon delivery of ADSC. Conclusion These results strongly indicate that administration of hiPSC-CM, unlike ADSC, preserve murine heart function in acute MI model. Additionally, overexpression of HO-1 may positively influence their survival upon in vivo delivery into infarcted tissue. Acknowledgement/Funding The National Centre for Research and Development (STRATEGMED 2/269415/11/NCBR/2015), National Science Centre of Poland (HARMONIA 2014/14/M/NZ1/00010)

scholarly journals Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

2016 ◽  
Vol 291 (33) ◽  
pp. 17066-17076 ◽  
Author(s):  
Carrie M. Elks ◽  
Peng Zhao ◽  
Ryan W. Grant ◽  
Hardy Hang ◽  
Jennifer L. Bailey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Cell Types ◽  
Oncostatin M ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Fat Feeding

Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMRFKO mice). The effects of OSM on gene expression were also assessed in vitro and in vivo. OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMRFKO mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMRFKO mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c. Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMRFKO mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.

scholarly journals Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 799 ◽  
Author(s):  
Joanna Lelek ◽  
Ewa K. Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

scholarly journals Stimulation of Innate Immunity byIn VivoCyclic di-GMP Synthesis Using Adenovirus

2014 ◽  
Vol 21 (11) ◽  
pp. 1550-1559 ◽  
Author(s):  
Benjamin J. Koestler ◽  
Sergey S. Seregin ◽  
David P. W. Rastall ◽  
Yasser A. Aldhamen ◽  
Sarah Godbehere ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mammalian Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Host Cells ◽  
Content Type ◽  
Cytokines And Chemokines ◽  
Novel Approach

ABSTRACTThe bacterial second messenger cyclic di-GMP (c-di-GMP) stimulates inflammation by initiating innate immune cell recruitment and triggering the release of proinflammatory cytokines and chemokines. These properties make c-di-GMP a promising candidate for use as a vaccine adjuvant, and numerous studies have demonstrated that administration of purified c-di-GMP with different antigens increases protection against infection in animal models. Here, we have developed a novel approach to produce c-di-GMP inside host cells as an adjuvant to exploit a host-pathogen interaction and initiate an innate immune response. We have demonstrated that c-di-GMP can be synthesizedin vivoby transducing a diguanylate cyclase (DGC) gene into mammalian cells using an adenovirus serotype 5 (Ad5) vector. Expression of DGC led to the production of c-di-GMPin vitroandin vivo, and this was able to alter proinflammatory gene expression in murine tissues and increase the secretion of numerous cytokines and chemokines when administered to animals. Furthermore, coexpression of DGC modestly increased T-cell responses to aClostridium difficileantigen expressed from an adenovirus vaccine, although no significant differences in antibody titers were observed. This adenovirus c-di-GMP delivery system offers a novel method to administer c-di-GMP as an adjuvant to stimulate innate immunity during vaccination.

scholarly journals Combination of Interleukin-27 and MicroRNA for Enhancing Expression of Anti-Inflammatory and Proosteogenic Genes

Arthritis ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Manoel Figueiredo Neto ◽  
Marxa L. Figueiredo
Keyword(s):  
Immune Cell ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Cell Types ◽  
Bone Cell ◽  
Inflammatory Gene Expression ◽  
Real Time Quantitative Pcr ◽  
Achievable Goal ◽  
Cell Balance

Remission of inflammation has become an achievable goal in inflammatory or rheumatoid arthritis (RA); however, bone erosion continues in many patients. Interleukin- (IL-) 27 regulates immune and bone cell balance and also suppresses activities of several inflammatory cell types in RA. Despite its promise, challenges to clinical translation of IL-27 have been its partial effects in vivo. Due to their ability to modulate plasticity of bone and immune cell differentiation, we examined the potential for several microRNA (miR) candidates in enhancing the effects of IL-27. Using differentiation, luciferase, and real time quantitative PCR assays, we show that IL-27 promotes osteoblast differentiation, reduces expression of osteoblast inhibitory genes, and reduces osteoclast differentiation, and results suggest a potential coordination with TGFβ/BMP/SMAD and JAK/STAT pathways. We selected miRNA regulators of these and related pathways to examine whether the effects of IL-27 could be augmented for therapeutic applications. miR-29b and miR-21 augmented IL-27 proosteogenic while downregulating osteoclastogenic signals and also worked to reduce inflammatory signaling in activated macrophages, while miR-21 and miR-20b worked with IL-27 to reduce inflammatory gene expression in fibroblasts and T cells. It appears that several miRNAs can be utilized to enhance IL-27’s impact on modulating osteogenesis and reducing proinflammatory signaling.

scholarly journals Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kassem Makki ◽  
Philippe Froguel ◽  
Isabelle Wolowczuk
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune Cells ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Cell Types ◽  
Immune Functions ◽  
Cytokines And Chemokines ◽  
Wide Range

Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field.

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