Treating murine inflammatory diseases with an anti-erythrocyte antibody

2019 ◽  
Vol 11 (506) ◽  
pp. eaau8217 ◽  
Author(s):  
Andrew R. Crow ◽  
Rick Kapur ◽  
Sandra Koernig ◽  
Ian K. Campbell ◽  
Chao-Ching Jen ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Transfer Model ◽  
Complement Components ◽  
Chemokine Production ◽  
Injury Model ◽  
Serum Transfer ◽  
Autoimmune And Inflammatory Diseases ◽  
Lung Injury Model

Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model of arthritis. Similarly, it rapidly reversed clinical disease progression in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis and completely corrected CAIA-induced increase in monocyte Fcγ receptor II/III expression. Ter119 dose-dependently induced plasma chemokines CCL2, CCL5, CXCL9, CXCL10, and CCL11 with corresponding alterations in monocyte percentages in the blood and liver within 24 hours. Ter119 attenuated chemokine production from the synovial fluid and prevented the accumulation of inflammatory cells and complement components in the synovium. Ter119 could also accelerate the resolution of hypothermia and pulmonary edema in an acute lung injury model. We conclude that this inflammatory anti-erythrocyte antibody simultaneously triggers a highly efficient anti-inflammatory effect with broad therapeutic potential.

scholarly journals The therapeutic potential and deleterious effect of glucocorticoids on AOM/DSS-induced colorectal cancer in mice

2021 ◽  
Author(s):  
Jun Pu ◽  
Xinrui Zhou ◽  
Jiaxin Liu ◽  
Peng Hou ◽  
Meiju Ji
Keyword(s):  
Colorectal Cancer ◽  
Body Weight ◽  
Deleterious Effect ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Tumor Formation ◽  
Jnk Pathway ◽  
Multiple Tumor ◽  
Autoimmune And Inflammatory Diseases

Abstract Background Glucocorticoids (GCs) are widely used in the treatment of various autoimmune and inflammatory diseases, including inflammatory bowel disease (IBD), but the effect of GCs on the development of colitis-associated colorectal cancer (CAC) is largely undefined. Methods We first established azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colorectal cancer and DSS-induced colitis in mice. Dexamethasone (DEX) was then administered at different periods of time to determine its effect on tumorigenesis and tumor progression. Moreover, body weight, stool property and fecal blood of mice were recorded. At the end of the study, the number and load of tumors were evaluated, and the expression of proteins associated with cell proliferation were measured. To evaluate the inflammation in colon, we detected the level of pro-inflammatory cytokine TNFα, and mucosal infiltration of inflammatory cells. Meanwhile, we also assessed the activity of MAPK/JNK pathway. Results AOM injection followed by three cycles of drinking water containing 1.5% DSS successfully induced multiple tumor formation in mouse colon and rectum. Both early and late DEX intervention suppressed tumor growth in mouse colorectum and significantly downregulated the expression of PCNA and cyclin D1. Meanwhile, DEX treatment significantly inhibited the TNFα production, mucosal infiltration of inflammatory cells and the activity of JNK pathway, which was more prominent in mice with early DEX intervention. However, DEX treatment deteriorated the general state of mouse manifested by greater loss of body weight and rectal bleeding. Conclusions Our data conclude that both early and late DEX intervention significantly ameliorate colonic inflammation and inhibit the development of AOM/DSS-induced colorectal cancer, at least partly due to the inhibition of MAPK/JNK pathway. However, the deleterious effect on the general condition of mouse may limit the duration of GCs treatment.

scholarly journals 7,7′-Dimethoxyagastisflavone Inhibits Proinflammatory Cytokine Release and Inflammatory Cell Recruitment through Modulating ERα Signaling

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1778
Author(s):  
Yi-Shin Wu ◽  
Chian-Ruei Chen ◽  
Yun-Ting Yeh ◽  
Han-Huei Lin ◽  
Yin-Hsuan Peng ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Estrogen Receptor Α ◽  
Multiple Organ ◽  
Confocal Imaging ◽  
Actin Assembly ◽  
Chemokine Production ◽  
Gene And Protein Expression ◽  
Inflammatory Macrophages

Acute systemic inflammatory diseases, including sepsis, usually result in cytokine disorder and multiple-organ failure. 7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus x media var. Hicksii, has previously been evaluated for its antiproliferative and antineoplastic effects in cancer cells. In this study, the effects of DMGF on the cytokine production and cell migration of inflammatory macrophages were investigated. The inhibition of cytokine and chemokine production by DMGF in LPS-treated macrophages was analyzed by a multiplex cytokine assay. Then, the integrin molecules used for cell adhesion and regulators of actin polymerization were observed by RT-PCR and recorded using confocal imaging. The DMGF interaction with estrogen receptor α (ERα) was modeled structurally by molecular docking and validated by an ERα reporter assay. DMGF inhibited TNF-α, IL-1β, and IL-6 production in LPS-induced macrophages. DMGF also inhibited inflammatory macrophage migration by downregulating the gene and protein expression of adhesion molecules (LFA-1 and VLA4) and regulators of actin assembly (Cdc42-Rac1 pathway). DMGF might interact with the ligand-binding domain of ERα and downregulate its transcriptional activity. These results indicated that DMGF effectively inhibited the production of proinflammatory cytokines and the recruitment of inflammatory cells through downregulating ERα signaling.

Treatment of Neurodegenerative Diseases with Bioactive Components ofTripterygium wilfordii

2019 ◽  
Vol 47 (04) ◽  
pp. 769-785 ◽  
Author(s):  
Jianheng Li ◽  
Jijun Hao
Keyword(s):  
Neurodegenerative Diseases ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Research Progress ◽  
Bioactive Components ◽  
Tripterygium Wilfordii Hook F ◽  
Autoimmune And Inflammatory Diseases ◽  
Tripterygium Wilfordii Hook

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.

IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses

Blood ◽  
2012 ◽  
Vol 119 (13) ◽  
pp. 3084-3096 ◽  
Author(s):  
Meryem Aloulou ◽  
Sanae Ben Mkaddem ◽  
Martine Biarnes-Pelicot ◽  
Tarek Boussetta ◽  
Hervé Souchet ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Activating Receptors ◽  
Autoimmune And Inflammatory Diseases ◽  
Continuous Interaction ◽  
Species Production ◽  
Activation Motif

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of several autoimmune and inflammatory diseases. However, its mechanism of action remains incompletely understood. Here, we investigated the possibility that IVIg induces its anti-inflammatory effects through activating Fcγ receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM) in the FcRγ signaling adaptor. Recently, the concept of inhibitory ITAM (ITAMi) has emerged as a new means to negatively control the immune response. We found that interaction of FcRγ-associated mouse or human FcγRIII with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab′)2 reduced calcium responses, reactive oxygen species production, endocytosis, and phagocytosis, induced by heterologous activating receptors on monocyte/macrophages and FcγRIII+ transfectants. Inhibition required the ITAMi configuration of the FcγRIII-associated FcRγ subunit and SHP-1 recruitment involving formation of intracellular “inhibisome” clusters containing FcγRIII, and the targeted heterologous activating receptor. IVIg as well as anti-FcγRIII treatments controlled the development of nonimmune mediated inflammation in vivo independently of FcγRIIB. These results demonstrate that circulating immunoglobulins (Ig)Gs are not functionally inert but act through continuous interaction with FcγRIII-inducing ITAMi signaling to maintain immune homeostasis. These data support a new mechanism of action for IVIg and demonstrate the therapeutic potential of FcγRIIIA targeting in inflammation.

scholarly journals Schistosome Infection and Schistosome-Derived Products as Modulators for the Prevention and Alleviation of Immunological Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Mu ◽  
Donald P. McManus ◽  
Nan Hou ◽  
Pengfei Cai
Keyword(s):  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
T Helper ◽  
T Helper 1 ◽  
Schistosome Infection ◽  
Parasitic Helminths ◽  
Parasite Survival ◽  
Autoimmune And Inflammatory Diseases ◽  
Human Immune ◽  
Considerable Period

Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It is now known that the degree of exposure to these and other pathogens inversely correlates with the incidence of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. Accordingly, there has been recent increased interest in utilizing active helminth worm infections and helminth-derived products for the treatment of human autoimmune and inflammatory diseases and to alleviate disease severity. Indeed, there is an accumulating list of novel helminth derived molecules, including proteins, peptides, and microRNAs, that have been shown to exhibit therapeutic potential in a variety of disease models. Here we consider the blood-dwelling schistosome flukes, which have evolved subtle immune regulatory mechanisms that promote parasite survival but at the same time minimize host tissue immunopathology. We review and discuss the recent advances in using schistosome infection and schistosome-derived products as therapeutics to treat or mitigate human immune-related disorders, including allergic asthma, arthritis, colitis, diabetes, sepsis, cystitis, and cancer.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Hacat Cells ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mapk Signaling Pathways ◽  
Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

scholarly journals Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
John N. Cronin ◽  
João Batista Borges ◽  
Douglas C. Crockett ◽  
Andrew D. Farmery ◽  
Göran Hedenstierna ◽  
...  
Keyword(s):  
Lung Injury ◽  
Dual Energy ◽  
Dual Energy Ct ◽  
Lung Density ◽  
Density Distributions ◽  
Single Slice ◽  
Injury Model ◽  
Lung Injury Model ◽  
Ct Density ◽  
Surfactant Depletion

Abstract Background Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified. Methods Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images. Results Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75–0.94) with agreement between CT density distributions (r 0.89–0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology. Conclusions Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

Sign in / Sign up

Export Citation Format

Share Document