With an antibody whose duty's double, a step towards ending asthma trouble?

2013 ◽  
Vol 451 (2) ◽  
pp. e1-e3
Author(s):  
Eric J. Sundberg
Keyword(s):  
Inflammatory Responses ◽  
Molecular Mimicry ◽  
Cell Signalling ◽  
Chronic Inflammatory Disease ◽  
Interleukin 4 ◽  
Receptor Interaction ◽  
Inflammatory Cascade ◽  
Treatment And Prevention ◽  
Il Interleukin

Asthma is a debilitating chronic inflammatory disease of the airways that results in shortness of breath, wheezing and coughing, often triggered by inhalation of common allergens. The prevalence and severity of asthma has increased dramatically over the last several decades to the point where several hundred million people worldwide are affected and each year tens of thousands of individuals die prematurely from asthma symptoms. The rise in disease prevalence is particularly evident in the developed world, where childhood exposure to bacteria and viruses has decreased dramatically, while the use of antibiotics, especially early in life, and births by Caesarean section have increased significantly; correlations that support the hygiene hypothesis. Central to the pathogenesis of asthma are the roles of TH2-type cytokines, including IL (interleukin)-4, IL-5, IL-9 and IL-13, in stimulating and perpetuating an inflammatory cascade that drives detrimental changes in airway structure and function. IL-4 and IL-13, in particular, have been targets of therapeutic development because, together, they specifically promote nearly all of the clinical features of asthma. Their inflammatory functions are highly complementary, but not identical, in large part because they share cell-surface receptors and transcription factors through which they stimulate cell signalling. In this issue of the Biochemical Journal, Redpath et al. have taken advantage of the shared receptor nature of the IL-4- and IL-13-mediated inflammatory responses to generate a novel antibody to the third ectodomain (D3) of IL-13Rα1 (IL-13 receptor α1), which forms a requisite binding site for both interleukins. This antibody potently neutralizes both IL-4 and IL-13 activities in vitro. Using X-ray crystallography complemented by molecular interaction and functional analyses, they clearly define its mechanism of dual cytokine neutralization as one of molecular mimicry of the interleukin–receptor interaction. Considering the complexity of the cytokine-mediated inflammatory cascade that defines asthma pathogenesis, such therapeutics that can effectively and simultaneously neutralize the actions of multiple cytokines and may play a significantly expanded role in the treatment and prevention of asthma in the future.

scholarly journals Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion

2012 ◽  
Vol 81 (1) ◽  
pp. 133-142 ◽  
Author(s):  
Martha Truscott ◽  
D. Andrew Evans ◽  
Matt Gunn ◽  
Karl F. Hoffmann
Keyword(s):  
Schistosoma Mansoni ◽  
Macrophage Activation ◽  
Inflammatory Responses ◽  
Interleukin 4 ◽  
Alternative Activation ◽  
Content Type ◽  
Hepatic Expression ◽  
Life Years ◽  
Alternatively Activated

The trematodeSchistosoma mansoniis one of the etiological agents of schistosomiasis, a key neglected tropical disease responsible for an estimated annual loss of 70 million disability-adjusted life years. Hematophagy represents the primary nutrient acquisition pathway of this parasite, but digestion of hemoglobin also liberates toxic heme. Schistosomes detoxify heme via crystallization into hemozoin, which is subsequently regurgitated into the host's circulation. Here we demonstrate that during experimental schistosomiasis, hemozoin accumulating in the mouse liver is taken up by phagocytes at a time coincident with the development of the egg-induced T-helper 2 (Th2) granulomatous immune response. Furthermore, the uptake of hemozoin also coincides with the hepatic expression of markers of alternative macrophage activation. Alternatively activated macrophages are a key effector cell population associated with protection against schistosomiasis, making hemozoin well placed to play an important immunomodulatory role in this disease. To systematically explore this hypothesis,S. mansonihemozoin was purified and added toin vitrobone marrow-derived macrophage cultures concurrently exposed to cytokines chosen to reflect the shifting state of macrophage activationin vivo. Macrophages undergoing interleukin-4 (IL-4)-induced alternative activation in the presence of hemozoin developed a phenotype specifically lacking inRetnla, a characteristic alternatively activated macrophage product associated with regulation of Th2 inflammatory responses. As such, in addition to its important detoxification role during hematophagy, we propose that schistosome hemozoin also provides a potent immunomodulatory function in the coevolved network of host-parasite relationships during schistosomiasis.

scholarly journals Gender Differences in Rheumatoid Arthritis: Interleukin-4 Plays an Important Role

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chaojie Yu ◽  
Chong Liu ◽  
Jie Jiang ◽  
Hao Li ◽  
Jiarui Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gender Differences ◽  
Cell Differentiation ◽  
Clinical Manifestations ◽  
Cell Receptor ◽  
Chronic Inflammatory Disease ◽  
Interleukin 4 ◽  
Receptor Interaction ◽  
Hub Genes ◽  
Kegg Pathways

Introduction. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical peripheral polyarthritis. A large number of studies have shown that RA is characterized by gender differences in clinical manifestations. The purpose of this study is to identify the key molecules of gender differences in patients with RA and to provide new molecular targets for personalized therapy. Material and Methods. The data from GSE55457 were downloaded from the comprehensive gene expression comprehensive database, and two groups (RA vs. No-RA groups, Male-RA vs. Female-RA groups) of differentially expressed genes (EDGs) were obtained by GEO2R. The GO function and KEGG pathway analyses of DEGs were carried out through the plug-in ClueGO in Cytoscape. Based on the STRING online, a protein-protein interaction (PPI) network was constructed. Hub genes were selected from CytoHubba. Through the intersection of the top 10 hub genes in two sets of EDGs, the key genes and related KEGG pathways were found. Quantitative Real-Time PCR and Western blotting analysis were performed for verification. Results. 1230 DEGs were screened between RA and No-RA groups, and 306 DEGs were screened between male and female RA groups. The common key gene of the two groups is IL-4. Between RA group and No-RA group, interleukin-4 (IL-4) participates in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, etc. Conclusion. This study contributes to the molecular biological mechanism of gender differences in RA. IL-4 may have played an important role.

Influence of BCG dose and age of inoculated mice on immunoprotection against tuberculosis and expression of IFN-γ/IL-4

2009 ◽  
Vol 6 (2) ◽  
pp. 171-176
Author(s):  
Guo Hui-Jun ◽  
Li Bao-Quan ◽  
Chai Jia-Qian ◽  
Chang Wei-Shan ◽  
Wang Chun-Yang ◽  
...  
Keyword(s):  
Low Dose ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
High Dose ◽  
Bacille Calmette Guerin ◽  
Il Interleukin ◽  
Cell Immunity ◽  
Ifn Γ ◽  
Old Mice

AbstractBalB/C neonate mice and adult BalB/C mice were vaccinated using BCG (Bacille Calmette–Guerin). The pathogenic growth characteristics of BCG in in vitro culture on spleen cells (SPC) were observed and changes in induced expression of IFN (interferon)-γ and IL (interleukin)-4 in SPC were detected using the ELISPOT assay. The results showed that a low dose of BCG (2×103 cfu) exerted 100% immunoprotection on 7-day-old neonate mice and a high dose of BCG (4×104 cfu) exerted 75% immunoprotection. A low dose of BCG (2×103 cfu) exerted 67% immunoprotection on 35-day-old mice. It is also shown that Th1-type cell immunity dominated by IFN-γ was enhanced significantly in the neonate mice injected with a low dose of BCG (2×103 cfu), and Th2-type cell immunity dominated by IL-4 was depressed at the same time. IFN-γ and IL-4 induced by a high dosage of BCG (4×104 cfu) in neonate mice were both increased. IFN-γ and IL-4 induced by a low dose of BCG (2×103 cfu) in 35-day-old mice were also increased. The results indicate that there exists a marked correlation between immunoprotection by BCG in mice and both the immunizing dose and age of the immune animals, which might be relevant to the changes induced by BCG on Th1- and Th2-type cell immunity.

scholarly journals Curative Anti-Inflammatory Properties of Chinese Optimized Yinxieling Formula in Models of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
RenRong Wei ◽  
Jing OuYang ◽  
WeiXian Lin ◽  
TongXiang Lin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Inflammatory Responses ◽  
Killer Cell ◽  
Glial Activation ◽  
Receptor Interaction ◽  
Therapeutic Benefits

Parkinson’s disease (PD) is marked by the progressive degeneration of dopaminergic neurons (DAN) accompanied by glial activation. Thus, inhibiting glial activation that occurs during this disease could be an effective method for treating PD. Optimized Yinxieling Formula (OYF), a Chinese medicinal formula, which is used to efficiently treat autoimmune disease psoriasis, has been proved to display potential immunomodulatory effects in inflammation-associated diseases. This study assessed the therapeutic benefits of OYF on glial-mediated neuroinflammation and neuroprotection in PD models in vitro and in vivo. First, the results showed that OYF significantly suppresses LPS-induced proinflammatory cytokine secretion and attenuates the overall inflammatory responses in BV-2 cells. Second, in vivo studies confirm that while the validity of our MPTP-induced PD mouse models possesses activated glia and significant neurobehavioral dysfunction, pretreatment with OYF prevents glial activation and ameliorates movement dysfunction in the MPTP-induced PD mouse models as evaluated by the pole and rotarod tests. Third, transcriptomic analyses were carried out to reveal the underlying molecular mechanism of the OYF treatment. Sixteen pathways were significantly upregulated in the OYF-treated PD model mice, including the cytokine-cytokine receptor interaction, cell adhesion molecules, coagulation, and complement cascades. Fifteen pathways were significantly downregulated in the OYF-treated PD model mice, such as the natural killer cell mediated cytotoxicity, hematopoietic cell lineage, phagosome, and others. These pathways share direct or indirect features of immunomodulation, suggesting that the physiological effects of OYF involve key roles of immune and inflammation regulations. Therefore, we prove that OYF is a useful immunomodulatory formula in developing prevention and treatment methods for neurodegenerative disease PD.

scholarly journals Comparison of Surface Functionalization of PLGA Composite to Immobilize Extracellular Vesicles

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3643
Author(s):  
Jiwon Woo ◽  
Kyoung-Won Ko ◽  
Seung-Gyu Cha ◽  
Yun Heo ◽  
Dong Keun Han
Keyword(s):  
Surface Modification ◽  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Covalent Bond ◽  
Bioactive Molecules ◽  
Receptor Interaction ◽  
Biodegradable Implants ◽  
Vitro Analysis ◽  
In Vitro Analysis

Endothelialization by materials provides a promising approach for the rapid re-endothelialization of a cardiovascular implantation. Although previous studies have focused on improving endothelialization through the immobilization of bioactive molecules onto the surface of biodegradable implants, comparative studies of effective surface modification have not yet been reported. Here, we conducted a comparative study on the surface modification of poly(lactide-co-glycolide) (PLGA)-based composites to graft mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) using three different materials, fibronectin (FN), polyethylenimine (PEI), and polydopamine (PDA), which have different bond strengths of ligand–receptor interaction, ionic bond, and covalent bond, respectively. Further in vitro analysis exhibited that MSC-EVs released from all modified films sustainably, but the MSC-EVs grafted onto the surface coated with PEI are more effective than other groups in increasing angiogenesis and reducing the inflammatory responses in endothelial cells. Therefore, the overall results demonstrated that PEI is a desirable coating reagent for the immobilization of MSC-EVs on the surface of biodegradable implants.

scholarly journals Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isaac J. Morrison ◽  
Jianan Zhang ◽  
Jingwen Lin ◽  
JeAnn E. Murray ◽  
Roy Porter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Nuclear Antigen ◽  
Artocarpus Heterophyllus ◽  
Dss Colitis ◽  
Treatment And Prevention ◽  
Human Cytochrome ◽  
Anti Inflammatory ◽  
Proliferating Cell

AbstractColorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.

Levels interleukine-4 and interleukin-17 (IL-4, IL-17) of blood in patients with habitual recurrent pregnancy loss, which occurred in a loop in vitro fertilization

2016 ◽  
pp. 137-139
Author(s):  
K.P. Golovatyuk ◽  
Keyword(s):  
In Vitro Fertilization ◽  
Conditioned Medium ◽  
Mononuclear Cells ◽  
Recurrent Miscarriage ◽  
Interleukin 4 ◽  
Control Group ◽  
Interleukin 17 ◽  
Vitro Fertilization ◽  
Blood Mononuclear Cells

The objective: was to investigate the levels of cytokines IL-4 and IL-17 in serum and conditioned medium cultures of blood mononuclear cells (MNC) and evaluation association between their products and miscarriage, which occurred in IVF cycles. Patients and methods. We observed 240 patients with recurrent miscarriage, came in IVF cycles, and 100 apparently healthy fertile women in the control group. The concentrations of IL-4 and IL-17 in serum and conditioned medium of MNC cultures were determined. Results. The levels of IL-4 in the serum and conditioned medium in spontaneous and stimulated mitogen secretion was not significantly different from those in the control group, whereas IL-17 levels were higher than those in the control group serum, in conditioned media of stimulated and non-stimulated MNCs. Conclusion. Disregulation of activity of circulating blood mononuclear cells in women with recurrent miscarriage that followed IVF, is accompanied by increased secretion of IL-17 and almost constant production of IL-4 on the back of high stimulation index of production of these cytokines. Key words: in vitro fertilization, miscarriage, interleukin-4, interleukin-17, serum stimulated and non-stimulated mononuclear blood.

Nanoparticles and Its Implications in HIV/AIDS Therapy

2020 ◽  
Vol 17 (4) ◽  
pp. 448-456 ◽  
Author(s):  
Victor B. Oti
Keyword(s):  
Direct Injection ◽  
Oral Intake ◽  
Public Health Problem ◽  
Antiretroviral Drugs ◽  
The Body ◽  
Viral Agent ◽  
Treatment And Prevention ◽  
Prevention And Treatment ◽  
Hiv Aids

The use of Antiretroviral drugs in treating HIV/ AIDS patients has enormously increased their life spans with serious disadvantages. The virus infection still remains a public health problem worldwide with no cure and vaccine for the viral agent until now. The use of nanoparticles (NPs) for the treatment and prevention of HIV/AIDS is an emerging technology of the 21st century. NPs are solid and colloid particles with 10 nm to <1000 nm size range; although, less than 200 nm is the recommended size for nanomedical usage. There are NPs with therapeutic capabilities such as liposomes, micelles, dendrimers and nanocapsules. The particle enters the body mainly via oral intake, direct injection and inhalation. It has been proven to have potentials of advancing the prevention and treatment of the viral agent. Certain NPs have been shown to have selftherapeutic activity for the virus in vitro. Strategies that are novel are emerging which can be used to improve nanotechnology, such as genetic treatment and immunotherapy. In this review, nanoparticles, the types and its characteristics in drug delivery were discussed. The light was furthermore shed on its implications in the prevention and treatment of HIV/AIDS.

Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells

2009 ◽  
Vol 417 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Munetoyo Toda ◽  
Risa Hisano ◽  
Hajime Yurugi ◽  
Kaoru Akita ◽  
Kouji Maruyama ◽  
...  
Keyword(s):  
Sialic Acid ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Signalling ◽  
Negative Regulator ◽  
Mammary Adenocarcinoma ◽  
Marginal Zone B Cells ◽  
Tumour Bearing

CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to α2,6- sialic acid-linked glycoconjugates, including a sialyl-Tn antigen that is one of the typical tumour-associated carbohydrate antigens expressed on various mucins. Many epithelial tumours secrete mucins into tissues and/or the bloodstream. Mouse mammary adenocarcinoma cells, TA3-Ha, produce a mucin named epiglycanin, but a subline of them, TA3-St, does not. Epiglycanin binds to CD22 and inhibits B-cell signalling in vitro. The in vivo effect of mucins in the tumour-bearing state was investigated using these cell lines. It should be noted that splenic MZ (marginal zone) B-cells were dramatically reduced in the mice bearing TA3-Ha cells but not in those bearing TA3-St cells, this being consistent with the finding that the thymus-independent response was reduced in these mice. When the mucins were administered to normal mice, a portion of them was detected in the splenic MZ associated with the MZ B-cells. Furthermore, administration of mucins to normal mice clearly reduced the splenic MZ B-cells, similar to tumour-bearing mice. These results indicate that mucins in the bloodstream interacted with CD22, which led to impairment of the splenic MZ B-cells in the tumour-bearing state.

Sign in / Sign up

Export Citation Format

Share Document