Ginsenoside Rb2 Ameliorates LPS-Induced Inflammation and ER Stress in HUVECs and THP-1 Cells via the AMPK-Mediated Pathway

Inflammation and endoplasmic reticulum (ER) stress have been documented to contribute to the development of atherosclerosis. Ginsenoside Rb2 has been reported to exhibit antidiabetic effects. However, the effects of Rb2 on atherosclerotic responses such as inflammation and ER stress in endothelial cells and monocytes remain unclear. In this study, the expression of inflammation and ER stress markers was determined using a Western blotting method. Concentrations of tumor necrosis factor alpha (TNF[Formula: see text]) and monocyte chemoattractant protein-1 (MCP-1) in culture media were assessed by enzyme-linked immunosorbent assay (ELISA) and apoptosis was evaluated by a cell viability assay and a caspase-3 activity measurement kit. We found that exposure of HUVECs and THP-1 monocytes to Rb2 attenuated inflammation and ER stress, resulting in amelioration of apoptosis and THP-1 cell adhesion to HUVECs under lipopolysaccharide (LPS) condition. Increased AMPK phosphorylation and heme oxygenase (HO)-1 expression, including GPR120 expression were observed in Rb2-treated HUVECs and THP-1 monocytes. Downregulation of both, AMPK phosphorylation and HO-1expression rescued these observed changes. Furthermore, GPR120 siRNA mitigated Rb2-induced AMPK phosphorylation. These results suggest that Rb2 inhibits LPS-mediated apoptosis and THP-1 cell adhesion to HUVECs by GPR120/AMPK/HO-1-associated attenuating inflammation and ER stress. Therefore, Rb2 can be used as a potential therapeutic molecule for treatment of atherosclerosis.

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Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000495926 ◽

2018 ◽

Vol 51 (6) ◽

pp. 2575-2590 ◽

Cited By ~ 15

Author(s):

Gang Zhong ◽

Ruiming Liang ◽

Jun Yao ◽

Jia Li ◽

Tongmeng Jiang ◽

...

Keyword(s):

Signaling Pathway ◽

Cruciate Ligament ◽

Interleukin 1 ◽

Cartilage Degradation ◽

Chondrocyte Apoptosis ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Viability Assay ◽

Necrosis Factor Alpha ◽

Anti Inflammatory

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide

Infection and Immunity ◽

10.1128/iai.73.8.4530-4538.2005 ◽

2005 ◽

Vol 73 (8) ◽

pp. 4530-4538 ◽

Cited By ~ 26

Author(s):

Tamika Burns ◽

Maria Abadi ◽

Liise-anne Pirofski

Keyword(s):

Monoclonal Antibody ◽

Inflammatory Response ◽

Capsular Polysaccharide ◽

Human Monoclonal Antibody ◽

Pneumococcal Infection ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1

ABSTRACT The human monoclonal antibody to serotype 8 pneumococcal capsular polysaccharide D11 [immunoglobulin M(κ)] protects wild-type and complement component 4 knockout (C4 KO) mice against lethal intratracheal challenge with serotype 8 pneumococcus, but it does not promote polymorphonuclear leukocyte (PMN)-mediated pneumococcal killing in vitro. In this study, we investigated the effect of D11 on the blood and lung bacterial burdens and the serum and lung expression of inflammatory chemokines and cytokines in an intratracheal challenge model with serotype 8 pneumococcus in C4 KO mice. Pneumococcus was not detected in the blood of D11-treated mice, whereas control mice had high-grade bacteremia with >107 CFU. Control mice had a >5-log increase in lung CFU and D11-treated mice manifested a nearly 3-log increase in lung CFU compared to the original inoculum 24 h after infection. Serum and lung levels of soluble macrophage inflammatory protein 2 (MIP-2) and interleulin-6 (IL-6) as measured by an enzyme-linked immunosorbent assay were lower in D11-treated mice than in control mice 24 h after infection. Real-time PCR was performed to examine lung mRNA chemokine and cytokine expression. The results showed that D11-treated mice had significantly less gamma interferon, MIP-2, IL-12, monocyte chemoattractant protein 1/JE, and tumor necrosis factor alpha expression than control mice 24 h after infection. Histopathology and immunohistochemical staining of lung tissues revealed that D11-treated mice had less inflammation, fewer PMNs, and less myeloperoxidase staining than control mice 24 h after infection. These findings suggest that the efficacy of certain serotype-specific antibodies against pneumococcal pneumonia could be associated with modulation of the lung inflammatory response and a reduction in host damage.

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Colonic Immunopathogenesis of Clostridium difficile Infections

Clinical and Vaccine Immunology ◽

10.1128/cvi.00770-13 ◽

2014 ◽

Vol 21 (4) ◽

pp. 509-517 ◽

Cited By ~ 20

Author(s):

Charles Darkoh ◽

Bradley P. Turnwald ◽

Hoonmo L. Koo ◽

Kevin W. Garey ◽

Zhi-Dong Jiang ◽

...

Keyword(s):

Clostridium Difficile ◽

Immunological Response ◽

Effector Memory ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Content Type ◽

Monocyte Chemoattractant Protein 1 ◽

Effector Memory T Cells ◽

Th1 And Th2 Cytokines ◽

Factor Alpha

ABSTRACTThere are major gaps in our understanding of the immunopathogenesis ofClostridium difficileinfections (CDIs). In this study, 36 different biomarkers were examined in the stools of CDI and non-CDI patients using the Proteome Profiler human cytokine array assay and quantitative enzyme-linked immunosorbent assay. Diarrheal stools from patients with CDI (CDI-positive diarrheal stools) showed higher relative amounts of the following inflammatory markers than the diarrheal stools from CDI-negative patients (CDI-negative diarrheal stools): C5a, CD40L, granulocyte colony-stimulating factor, I-309, interleukin-13 (IL-13), IL-16, IL-27, monocyte chemoattractant protein 1, tumor necrosis factor alpha, and IL-8. IL-8 and IL-23 were present in a larger number of CDI-positive diarrheal stools than CDI-negative diarrheal stools. Th1 and Th2 cytokines were not significantly different between the CDI-positive and CDI-negative diarrheal stools. Lactoferrin and calprotectin concentrations were also higher in the CDI-positive diarrheal stools. Our results demonstrate that CDI elicits a proinflammatory host response, and we report for the first time that IL-23 is a major marker in CDI-positive diarrheal stools. IL-23 may explain the lack of a robust immunological response exhibited by a proportion of CDI patients and may relate to recurrence; the IL-23 levels induced during CDI in these patients may be inadequate to sustain the cellular immunity conferred by this cytokine in promoting the induction and proliferation of effector memory T cells.

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Cytokine Profiling of Macrophages Exposed to Porphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

Infection and Immunity ◽

10.1128/iai.73.2.935-943.2005 ◽

2005 ◽

Vol 73 (2) ◽

pp. 935-943 ◽

Cited By ~ 147

Author(s):

Qingde Zhou ◽

Tesfahun Desta ◽

Matthew Fenton ◽

Dana T. Graves ◽

Salomon Amar

Keyword(s):

Porphyromonas Gingivalis ◽

Peritoneal Macrophages ◽

Cytokine Profile ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Antibody Arrays ◽

Mouse Peritoneal Macrophages

ABSTRACT To characterize the roles of Porphyromonas gingivalis and its components in the disease processes, we investigated the cytokine profile induced by live P. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found that P. gingivalis LPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to live P. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by live P. gingivalis, but not by P. gingivalis LPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced by P. gingivalis LPS or FimA, but not by live P. gingivalis. In vivo, IL-6 mRNA was strongly induced only by live P. gingivalis while monocyte chemoattractant protein 1 mRNA was strongly induced only by P. gingivalis LPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)- and TLR4-deficient macrophages revealed that most of the cytokines induced by P. gingivalis LPS or FimA signal through TLR2, while most of cytokines induced by live P. gingivalis signal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by live P. gingivalis inhibited the release of RANTES, VCAM-1, and IL-1α from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed that P. gingivalis LPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense live P. gingivalis and its components differently, which translates into the expression of different inflammatory cytokine profiles.

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Predictor value of the inflammation biomarkers regarding the post-infarction remodeling of myocardium

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2018-5-17-24 ◽

2018 ◽

Vol 17 (5) ◽

pp. 17-24

Author(s):

M. V. Ivanov ◽

M. I. Popovich ◽

L. M. Cheban ◽

I. M. Popovich ◽

V. M. Ivanov ◽

...

Keyword(s):

Prognostic Value ◽

Inflammatory Biomarkers ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

St Segment Elevation ◽

Anti Inflammatory ◽

Myocardium Remodeling ◽

Remodeling Pattern

Aim.To study the trait of the changes of circulating level of pro- and antiinflammatory biomarkers as well as metalloproteinase 8 (MMP-8) in the first 7 days after revascularization in patients with acute myocardial infarction with ST segment elevation (STEMI) for assessment of their prognostic value regarding post-infarction remodeling pattern.Material and methods.In 113 patients with STEMI which developed in 5 months after angioplasty adaptive myocardium remodeling (AMR) (n=56) or pathological myocardium remodeling (PMR) (n=57), determined by enzyme-linked immunosorbent assay (ELISA) method daily serum concentration of pro-inflammatory ((high sensitive C reactive protein, interleukins (IL) 1, 6, tumor necrosis factor alpha and monocyte chemoattractant protein 1)), anti-inflammatory biomarkers (IL-4, IL-10, IL-33, IL-1 receptor antagonist and heregulin-1beta) аs well as ММР-8 in the first 7 days after myocardium revascularization. According to clinic-demographic indices both groups were comparable. Obtained data have been compared with results of 20 healthy persons (control group).Results.The dynamics of pro-inflammatory biomarkers did not differ in patients with AMR and PMR after revascularization. It was characterized by a significant biomarker increase at 3-rd day followed by a decline toward 7-th day up to initial level. Among anti-inflammatory biomarkers IL-4 and IL-10 have manifested by a distinct dynamic in concern to myocardial remodeling pattern. In both groups these interleukins decreased after angioplasty, reaching a minimal level at 3-rd day. However, in patients with AMR since 4-th day has been established an increase of serum content of IL-4 and IL-10, their increment being at 7-th day in a range of 52-55% (p<0,05). In patients with PMR the interleukins rise was negligible: 5,7-5,8%. MMP-8 dynamics also has been different in groups and was correlated with dynamics of IL-4 and IL-10. Thus, in patients with AMR its level has fallen since 4-th day up to 7-th day by 46,6%, while in group with PMR metalloproteinase level in this period practically did not change, remaining significantly higher than control by 45-53%.Conclusion.In our study the serum content of main pro-inflammatory biomarkers (hsCRP, IL-1, IL-6, TNF-ɑ) didn’t differ in the first 7 days after revascularization in patients with adaptive and pathological postinfarction remodeling of myocardium, and thus don’t have predictive value concerning the remodeling pattern. Among anti-inflammatory cytokines dynamics of IL-4 and IL-10 differed in dependence on remodeling pattern. Their significant elevation by 52-55% from 4th up to 7th day after angioplasty was established in patients with adaptive myocardium remodeling, while in PMR their level didn’t change during this period that can emphasize their prognostic value. The character of MMP-8 change is pathogenetically correlated with dynamics of IL-4 and IL-10.

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Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence of Aspergillus fumigatus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01095-06 ◽

2006 ◽

Vol 51 (3) ◽

pp. 1048-1054 ◽

Cited By ~ 34

Author(s):

M. Simitsopoulou ◽

E. Roilides ◽

C. Likartsis ◽

J. Ioannidis ◽

A. Orfanou ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Enzyme Linked Immunosorbent Assay ◽

Rt Pcr ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Human Monocytic Cell Line ◽

Cytokines And Chemokines ◽

Human Monocytic Cell

ABSTRACT We assessed the effect of voriconazole (VRC) on the expression and release of selected cytokines and chemokines in the THP-1 human monocytic cell line in response to Aspergillus fumigatus hyphal fragments (HF) by cDNA microarray analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay. Stimulation of THP-1 cells by HF alone caused a significant up-regulation of CCL4 (MIP1B) and CCL16, while CCL2 (MCP1) was down-regulated. By comparison, in the presence of VRC, a large number of genes such as CCL3 (MIP1A), CCL4 (MIP1B), CCL5 (RANTES), CCL7 (MCP3), CCL11 (EOTAXIN), CCL15 (MIP1Δ), CXCL6, and CXCL13 were strongly up-regulated in THP-1 cells challenged by HF, whereas CCL20 (MIP3A) and CCL21 (MIP2) were down-regulated. Among five genes differentially expressed in THP-1 cells, IL12A, IL12B, and IL-16 were down-regulated whereas IL-11 and TGFB1 were significantly up-regulated in the presence of VRC. The inflammation-related genes IFNγ, IL1R1, and TNFA were also up-regulated in THP-1 cells exposed to HF only in the presence of VRC. RT-PCR of four selected genes validated the results of microarrays. The release of interleukin 1β (IL-1β) and IL-12 was significantly increased from monocytes stimulated either by HF alone (P < 0.05) or in the presence of VRC (P < 0.01 and P < 0.05, respectively). In contrast, tumor necrosis factor alpha release from monocytes was enhanced only in the presence of VRC (P < 0.01). The chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β were decreased under both conditions (P < 0.01). These results demonstrate that in the presence of VRC, HF induces a more pronounced profile of gene expression in THP-1 cells than HF alone, potentially leading to more-efficient host resistance to A. fumigatus.

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Recombinant γY278H Fibrinogen Showed Normal Secretion from CHO Cells, but a Corresponding Heterozygous Patient Showed Hypofibrinogenemia

International Journal of Molecular Sciences ◽

10.3390/ijms22105218 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5218

Author(s):

Tomu Kamijo ◽

Takahiro Kaido ◽

Masahiro Yoda ◽

Shinpei Arai ◽

Kazuyoshi Yamauchi ◽

...

Keyword(s):

Cell Lines ◽

Cho Cells ◽

Fibrinogen Level ◽

Culture Media ◽

Chinese Hamster ◽

Plasma Fibrinogen ◽

Enzyme Linked Immunosorbent Assay ◽

Cho Cell ◽

Accelerated Degradation ◽

Heterozygous Patient

We identified a novel heterozygous hypofibrinogenemia, γY278H (Hiroshima). To demonstrate the cause of reduced plasma fibrinogen levels (functional level: 1.12 g/L and antigenic level: 1.16 g/L), we established γY278H fibrinogen-producing Chinese hamster ovary (CHO) cells. An enzyme-linked immunosorbent assay demonstrated that synthesis of γY278H fibrinogen inside CHO cells and secretion into the culture media were not reduced. Then, we established an additional five variant fibrinogen-producing CHO cell lines (γL276P, γT277P, γT277R, γA279D, and γY280C) and conducted further investigations. We have already established 33 γ-module variant fibrinogen-producing CHO cell lines, including 6 cell lines in this study, but only the γY278H and γT277R cell lines showed disagreement, namely, recombinant fibrinogen production was not reduced but the patients’ plasma fibrinogen level was reduced. Finally, we performed fibrinogen degradation assays and demonstrated that the γY278H and γT277R fibrinogens were easily cleaved by plasmin whereas their polymerization in the presence of Ca2+ and “D:D” interaction was normal. In conclusion, our investigation suggested that patient γY278H showed hypofibrinogenemia because γY278H fibrinogen was secreted normally from the patient’s hepatocytes but then underwent accelerated degradation by plasmin in the circulation.

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Interleukin-6 via Toll-Like Receptor 3 Signaling Attenuates the Expression of Proinflammatory Chemokines in Human Podocytes

Kidney & Blood Pressure Research ◽

10.1159/000514589 ◽

2021 ◽

Vol 46 (2) ◽

pp. 207-218

Author(s):

Hidenori Umetsu ◽

Shojiro Watanabe ◽

Tadaatsu Imaizumi ◽

Tomomi Aizawa ◽

Koji Tsugawa ◽

...

Keyword(s):

Rna Interference ◽

Molecular Mechanisms ◽

Kidney Diseases ◽

Enzyme Linked Immunosorbent Assay ◽

Toll Like Receptor ◽

Induced Expression ◽

Inflammatory Reactions ◽

Monocyte Chemoattractant Protein 1 ◽

Polycytidylic Acid ◽

Tlr3 Signaling

Background: Although toll-like receptor 3 (TLR3) signaling is involved in the development of certain chronic kidney diseases, the specific molecular mechanisms underlying inflammatory reactions via activation of TLR3 signaling in human podocytes remain unclear. Interleukin (IL)-6 is a pleiotropic cytokine associated with innate and adaptive immune responses; however, little is known about the implication of IL-6 via the activation of regional TLR3 signaling in the inflammatory reactions in human podocytes. Methods: We treated immortalized human podocytes with polyinosinic-polycytidylic acid (poly IC), an authentic viral double-stranded RNA, and assessed the expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5) using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against IFN-β and IL-6. Results: We found that the activation of TLR3 induced expression of IL-6, MCP-1, CCL5, and IFN-β in human podocytes. RNA interference experiments revealed that IFN-β was involved in the poly IC-induced expression of IL-6, MCP-1, and CCL5. Interestingly, IL-6 knockdown markedly increased the poly IC-induced expression of MCP-1 and CCL5. Further, treatment of cells with IL-6 attenuated the expression of CCL5 and MCP-1 mRNA and proteins. Conclusion: IL-6 induced by TLR3 signaling negatively regulates the expression of representative TLR3 signaling-dependent proinflammatory chemokines in human podocytes.

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Gene engineered mesenchymal stem cells: greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02245-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maria Florian ◽

Jia-Pey Wang ◽

Yupu Deng ◽

Luciana Souza-Moreira ◽

Duncan J. Stewart ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Transgene Expression ◽

Vascular Inflammation ◽

Pulmonary Inflammation ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Therapeutic Benefits

Abstract Background Acute lung injury (ALI) and in its severe form, acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance the potency of mesenchymal stem cells (MSCs) to develop more effective treatments. Genetic modification of MSCs has been demonstrated to significantly improve the therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off-target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration. Methods Here, we explored whether a minicircle DNA (MC) vector containing human angiopoietin 1 (MC-ANGPT1) can provide a more effective platform for gene-enhanced MSC therapy of ALI/ARDS. Results At 24 h after transfection, nuclear-targeted electroporation using an MC-ANGPT1 vector resulted in a 3.7-fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048 ± 567 pg/mL vs. 552.1 ± 33.5 pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSCs significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSCs reduced it by 71% (p < 0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSCs significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). pANGPT1-transfected MSCs significantly reduced BAL albumin levels by 71%, while MC-ANGPT1-transfected MSCs reduced it by 85%. Conclusions Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSCs and enhanced the therapeutic effect on the ALI model compared to plasmid. These results support the potential benefits of MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.

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Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

Endocrine Reviews ◽

10.1210/edrv.30.7.9995 ◽

2009 ◽

Vol 30 (7) ◽

pp. 928-928

Author(s):

Guenther Boden ◽

Matthew Silviera ◽

Brian Smith ◽

Peter Cheung ◽

Carol Homko

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Tissue Injury ◽

Subcutaneous Fat ◽

Whole Body ◽

Monocyte Chemoattractant Protein 1 ◽

Homologous Protein ◽

Stress Markers ◽

Acute Tissue Injury ◽

Glucose Regulated Protein

Abstract Background It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress. Objective Our objective was to determine whether open, sc fat biopsies cause ER stress. Approach Five healthy subjects underwent three open sc fat biopsies. The first biopsy, taken from the lateral aspect of a thigh, was followed 4 h later by a second biopsy from the same incision site and a third biopsy from the contralateral leg. Expression markers of ER stress, inflammation, hypoxia, and adipokines were measured in these fat biopsies. In addition, we tested for signs of systemic ER stress and inflammation in plasma and in circulating monocytes. Results mRNA/18s ratios of IL-6, monocyte chemoattractant protein-1, CD-14, hypoxia-induced factor 1-α, the spliced form of Xbox protein-1, glucose-regulated protein 78, CEBP homologous protein, and activating factor-4 were all severalfold higher, whereas mRNA/18s ratios of adiponectin and leptin were lower in fat biopsies taken from the same site 4 h after the first biopsy but were unchanged in the second biopsy that was taken from the contralateral site. The biopsies were not associated with changes in plasma and monocyte IL-6 concentrations or in monocyte ER stress markers. Also, whole-body insulin-stimulated glucose uptake was the same in 15 subjects who had biopsies compared with 15 different subjects who did not. Conclusion Open, sc fat biopsies produced inflammation, hypoxia, ER stress, and decreased expression of adiponectin and leptin. These changes remained confined to the biopsy site for at least 4 h.

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