scholarly journals Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases

2021 ◽  
Vol 22 (20) ◽  
pp. 11136
Author(s):  
Xiaojie Chu ◽  
Zehua Sun ◽  
Du-San Baek ◽  
Wei Li ◽  
John W. Mellors ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Lung Diseases ◽  
Inflammatory Diseases ◽  
Human Antibody ◽  
Peptide Arrays ◽  
Inhibitory Effects ◽  
Immunotherapy Of Cancer ◽  
Human Igg1 ◽  
Cancer And Inflammation ◽  
Lung Tissue Damage

Neutrophil elastase (NE) is a serine protease released during neutrophil maturation. High levels of NE are related to lung tissue damage and poor prognosis in cancer; thus, NE is a potential target for therapeutic immunotherapy for multiple lung diseases and cancers. Here, we isolate and characterize two high-affinity, specific, and noncompetitive anti-NE antibodies Fab 1C10 and VH 1D1.43 from two large phage-displayed human Fab and VH libraries. After fusion with human IgG1 Fc, both of them (VH-Fc 1D1.43 and IgG1 1C10) inhibit NE enzymatic activity with VH-Fc 1D1.43 showing comparable inhibitory effects to that of the small molecule NE inhibitor SPCK and IgG1 1C10 exhibiting even higher (2.6-fold) activity than SPCK. Their epitopes, as mapped by peptide arrays combined with structural modeling, indicate different mechanisms for blocking NE activity. Both VH-Fc and IgG1 antibodies block NE uptake by cancer cells and fibroblast differentiation. VH-Fc 1D1.43 and IgG1 1C10 are promising for the antibody-based immunotherapy of cancer and inflammatory diseases.

Immunopharmacological Activity of Betulin in Inflammation-associated Carcinogenesis

2018 ◽  
Vol 18 (5) ◽  
pp. 645-651 ◽  
Author(s):  
Anja Schwiebs ◽  
Heinfried H. Radeke
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Dual Function ◽  
Special Focus ◽  
Birch Bark ◽  
Pentacyclic Triterpene ◽  
Cancer And Inflammation ◽  
Potential Use

This review highlights the multiple properties of the birch bark-derived pentacyclic triterpene betulin with special focus on its pharmacological activity in cancer and inflammation. While less well characterized compared to its hydrophilic derivative, betulinic acid, it exhibits potent anticancer activity described in many publications. Indeed, underinvestigated are its immunomodulatory functions in inflammatory diseases that appeared to enhance innate immune cell activities in an adjuvant-like fashion towards an interleukin-12 driven antitumor immunity. Herein, we like to emphasize the simultaneous and dual function of betulin on the basis of recent investigations of the tumor microenvironment and enlighten the potential use of betulin in the control of inflammation-associated carcinogenesis.

Synthesis, characterization and inhibitory effects of crocetin derivative compounds in cancer and inflammation

2018 ◽  
Vol 98 ◽  
pp. 157-164 ◽  
Author(s):  
Yang Chu ◽  
Jin Gao ◽  
Jie Niu ◽  
Yan-Fen Huang ◽  
Ming Chen ◽  
...  
Keyword(s):  
Inhibitory Effects ◽  
Cancer And Inflammation

The Molecular targets of Cannabinoids in the treatment of Cancer and Inflammation

2021 ◽  
Vol 27 ◽  
Author(s):  
Alenabi Aylar ◽  
Malekinejad Hassan
Keyword(s):  
Cannabinoid Receptors ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Anticancer Effects ◽  
Anti Cancer ◽  
Culture Models ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Objective: In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas and hepatic cancers. The anticancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cells migration, suppression of vascularization and induction of apoptosis. Conclusion: The current review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

scholarly journals Bioactive Plant Compounds in Coffee Charcoal (Coffeae carbo) Extract Inhibit Cytokine Release from Activated Human THP-1 Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4263 ◽  
Author(s):  
Weber ◽  
Hammoud Mahdi ◽  
Jankuhn ◽  
Lipowicz ◽  
Vissiennon
Keyword(s):  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Inflammatory Diseases ◽  
Cytokine Signaling ◽  
Phytochemical Analysis ◽  
Inhibitory Effects ◽  
Plant Metabolites ◽  
Electron Microscopic ◽  
Secondary Plant Metabolites ◽  
Secondary Plant

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.

scholarly journals ANTIOXIDANT-VITAMIN C: LUNG FUNCTION; LUNG CANCER

2016 ◽  
pp. 43
Author(s):  
Mazahar Farooqui ◽  
Rajendra Pardeshi ◽  
Santosh Jadhav
Keyword(s):  
Lung Cancer ◽  
Lung Function ◽  
Vitamin C ◽  
Lung Tissue ◽  
Lung Diseases ◽  
Daily Life ◽  
Antioxidant Vitamin ◽  
Vegetables And Fruits ◽  
The Relationship ◽  
Lung Tissue Damage

<p>ABSTRACT<br />Non-enzymatic vitamin C (ascorbic acid) plays an important role in the medicinal field and acts as antioxidants use in fruits and vegetable such as<br />lemon, orange, grapes, carrots, tomatoes, grapefruit, beans, broccoli, and mangos. It helps to prevent and stop of various diseases such as lung cancer,<br />asthma, and wheezing and finding an antibronchospastic effect. Other factors such as diet have also been implicated in the development of lung<br />cancer. Despite the extensive research conducted in this area, the relationship between diet and lung cancer is still not clear. Diets high in fat and<br />low in vegetables and fruits may increase the risk of lung cancer and other fact eating of tobacco and smoking of cigarette. Lung tissue damage due<br />to high levels of free radicals in cigarette smoke causes direct (tissue oxidation) and indirect (release of oxidizing agents and enzymes). Vitamin C is<br />necessary for phagocytosis. It plays a significant role in daily life, dietary system like eating food, vegetable and smoking of cigarette. It helps to prevent<br />or stop the damage the lung tissue/or cause lung cancer. The present review studied that application of vitamin C act as antioxidant in lung cancer like<br />diseases such as lung-cancer and role in lung function.<br />Keywords: Review, Non-enzymatic antioxidant (vitamin C), Lung function, Lung diseases.</p>

scholarly journals Contribution of Host Defence Proteins and Peptides to Host-Microbiota Interactions in Chronic Inflammatory Lung Diseases

Vaccines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 49 ◽  
Author(s):  
Anne van der Does ◽  
Gimano Amatngalim ◽  
Bart Keijser ◽  
Pieter Hiemstra ◽  
Remi Villenave
Keyword(s):  
Respiratory Tract ◽  
Lung Diseases ◽  
Inflammatory Diseases ◽  
Host Defence ◽  
Therapeutic Approaches ◽  
Defence Proteins ◽  
Novel Therapeutic Strategies ◽  
Gut Microbiota Composition ◽  
Respiratory Microbiota

The respiratory tract harbours a variety of microorganisms, collectively called the respiratory microbiota. Over the past few years, alterations in respiratory and gut microbiota composition have been associated with chronic inflammatory diseases of the lungs. How these changes influence disease development and progression is an active field of investigation. Identifying and understanding host-microbiota interactions and factors contributing to these interactions could promote the development of novel therapeutic strategies aimed at restoring host-microbiota homeostasis. In this review, we discuss recent literature on host-microbiota interactions in the respiratory tract, with a specific focus on the influence of endogenous host defence peptides and proteins (HDPs) on the composition of microbiota populations in vivo and explore possible HDPs-related therapeutic approaches targeting microbiota dysbiosis in chronic inflammatory lung diseases.

Migratory responses of PMN after intraperitoneal and intratracheal administration of lipopolysaccharide

1996 ◽  
Vol 270 (5) ◽  
pp. L836-L845 ◽  
Author(s):  
S. Hirano
Keyword(s):  
Intraperitoneal Injection ◽  
Lung Diseases ◽  
Polymorphonuclear Leukocytes ◽  
Intratracheal Instillation ◽  
Sublethal Dose ◽  
Inhibitory Effects ◽  
Mixed Cell ◽  
Intratracheal Administration ◽  
Necrosis Factor ◽  
Factor Concentration

The present study was undertaken primarily to investigate accumulation of polymorphonuclear leukocytes (PMN) within the lung vasculature after intraperitoneal injection of lipopolysaccharide (LPS) and migratory responses of those intravascular PMN to intratracheally instilled LPS in mice. Intraperitoneally injected LPS was absorbed into the blood rapidly, and the concentration of circulating LPS peaked at 1 h postinjection. Tumor necrosis factor concentration in blood began to increase at 0.5 h and also peaked at 1 h postinjection. The number of lung vascular-associated PMN was increased 7.5-fold at 0.5 h post-intraperitoneal injection. However, neither diapedesis of PMN nor injury was observed in the lung, while mixed cell infiltration was observed in the liver. Although intraperitoneally injected LPS caused a significant PMN accumulation within the lung vasculature, pre-intraperitoneal injection of LPS dramatically and dose dependently abolished both intratracheal LPS-inducible PMN infiltration and apparent plasma protein leakage into the alveolar space. On the other hand, pre-intratracheal instillation of LPS enhanced rather than reduced intraperitoneal LPS-inducible PMN infiltration into the peritoneal cavity. In rats, a sublethal dose of intraperitoneally injected LPS caused a modest increase in alveolar PMN and yet reduced intratracheal LPS-inducible robust transpulmonary PMN infiltration. Although mechanisms of different migratory responses of the lung vasculature-associated PMN are unknown, the inhibitory effects of intraperitoneally injected LPS on transpulmonary PMN infiltration may be applicable to treatments for septic lung diseases.

Oxidation-resistant variants of recombinant anti-leucoprotease are better inhibitors of human-neutrophil-elastase-induced emphysema in hamsters than natural recombinant antileucoprotease

1991 ◽  
Vol 81 (6) ◽  
pp. 777-784 ◽  
Author(s):  
A. Rudolphus ◽  
R. Heinzel-Wieland ◽  
V. A. M. M. Vincent ◽  
D. Saunders ◽  
G. J. Steffens ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Site Directed Mutagenesis ◽  
Human Neutrophil Elastase ◽  
Polymorphonuclear Leucocytes ◽  
Inhibitory Effects ◽  
Oxidative Inactivation ◽  
Methionine Residues

1. Antileucoprotease, being sensitive to oxidative inactivation, can be produced by recombinant techniques. Via site-directed mutagenesis, two mutants of recombinant antileucoprotease were produced in which one or more of the oxidation-sensitive methionine residues were replaced by leucine: in rALP242, methionine-73 was replaced by leucine, and in rALP231, leucine was substituted for four methionine residues. In vitro, native antileucoprotease and the recombinant antileucoprotease preparations have similar inhibitory characteristics towards human neutrophil elastase. We hypothesized that replacement of methionine residues in the antileucoprotease molecule would result in a reduced oxidation sensitivity of the mutants. 2. After incubation of recombinant antileucoprotease and its mutants with increasing dosages of cis-platinum(II)diammine dichloride, we observed that native antileucoprotease and recombinant antileucoprotease were inactivated by this reagent to the same extent. Compared with this, rALP242 was less inactivated, whereas the inhibitory capacity of rALP231 was not influenced by cis-platinum(II)diammine dichloride at all. 3. After incubation of recombinant antileucoprotease, rALP242 and rALP231 with triggered polymorphonuclear leucocytes, which are thought to produce an excess of oxidants, we measured residual inhibitory activities towards human neutrophil elastase of 10%, 55% and 87%, respectively. 4. In vivo, the inhibitory effects of intratracheally administered rALP242 and rALP231 towards human-neutrophil-elastase-induced emphysema were significantly greater than that of recombinant antileucoprotease. There were no significant differences between the mutants. With respect to secretory cell metaplasia and haemorrhage, rALP231 tended to be a better inhibitor than recombinant antileucoprotease and rALP242. 5. We conclude that the recombinant antileucoprotease mutants are less sensitive to oxidation and consequently inhibit human-neutrophil-elastase-induced emphysema to a greater extent than recombinant antileucoprotease.

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