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Journal of Immunology Research 2016Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides... (Review)
Review
Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides produced by a number of cell types, most notably neutrophil granulocytes and epithelial cells. All three defensin types (-, -, and -defensins) have antibacterial activities, mainly through bacterial membrane permeabilization. Defensins are effective against Gram-negative and Gram-positive bacteria including mycobacteria and are active both intra- and extracellularly. Mycobacterial resistance has never been demonstrated although the gene encoding resistance in is present in the genome. In addition to their antibacterial effect, defensins are chemoattractants for macrophages and neutrophils. There are many cases for their use for therapy or prophylaxis in tuberculosis as well. In conclusion, we propose that there is considerable scope and potential for exploring their use as therapeutic/prophylactic agents and more comprehensive survey of defensins from different species and their bioactivity is timely.
Topics: Animals; Anti-Bacterial Agents; Defensins; Host-Pathogen Interactions; Humans; Immunity; Mycobacterium; Mycobacterium Infections
PubMed: 27725944
DOI: 10.1155/2016/7515687 -
Cells Nov 2021Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against... (Review)
Review
Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.
Topics: Biomarkers; Disease; Epithelium; Humans; Immunity; Organ Specificity; beta-Defensins
PubMed: 34831214
DOI: 10.3390/cells10112991 -
Biological Chemistry Sep 2017Defensins, as a prominent family of antimicrobial peptides (AMP), are major effectors of the innate immunity with a broad range of immune modulatory and antimicrobial... (Review)
Review
Defensins, as a prominent family of antimicrobial peptides (AMP), are major effectors of the innate immunity with a broad range of immune modulatory and antimicrobial activities. In particular, defensins are the only recognized fast-response molecules that can neutralize a broad range of bacterial toxins, many of which are among the deadliest compounds on the planet. For a decade, the mystery of how a small and structurally conserved group of peptides can neutralize a heterogeneous group of toxins with little to no sequential and structural similarity remained unresolved. Recently, it was found that defensins recognize and target structural plasticity/thermodynamic instability, fundamental physicochemical properties that unite many bacterial toxins and distinguish them from the majority of host proteins. Binding of human defensins promotes local unfolding of the affected toxins, destabilizes their secondary and tertiary structures, increases susceptibility to proteolysis, and leads to their precipitation. While the details of toxin destabilization by defensins remain obscure, here we briefly review properties and activities of bacterial toxins known to be affected by or resilient to defensins, and discuss how recognized features of defensins correlate with the observed inactivation.
Topics: Bacterial Toxins; Defensins; Humans; Protein Conformation; Thermodynamics
PubMed: 28593905
DOI: 10.1515/hsz-2017-0106 -
Angewandte Chemie (International Ed. in... Sep 2014Cyclic peptides are found in a diverse range of organisms and are characterized by their stability and role in defense. Why is only one class of cyclic peptides found in... (Review)
Review
Cyclic peptides are found in a diverse range of organisms and are characterized by their stability and role in defense. Why is only one class of cyclic peptides found in mammals? Possibly we have not looked hard enough for them, or the technologies needed to identify them are not fully developed. We also do not yet understand their intriguing biosynthesis from two separate gene products. Addressing these challenges will require the application of chemical tools and insights from other classes of cyclic peptides. Herein, we highlight recent developments in the characterization of theta defensins and describe the important role that chemistry has played in delineating their modes of action. Furthermore, we emphasize the potential of theta defensins as antimicrobial agents and scaffolds for peptide drug design.
Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Defensins; Drug Design; Humans; Models, Molecular; Molecular Sequence Data; Peptides, Cyclic
PubMed: 25079086
DOI: 10.1002/anie.201402167 -
Biochemical Society Transactions Feb 2022Defensins are a class of host defence peptides (HDPs) that often harbour antimicrobial and anticancer activities, making them attractive candidates as novel... (Review)
Review
Defensins are a class of host defence peptides (HDPs) that often harbour antimicrobial and anticancer activities, making them attractive candidates as novel therapeutics. In comparison with current antimicrobial and cancer treatments, defensins uniquely target specific membrane lipids via mechanisms distinct from other HDPs. Therefore, defensins could be potentially developed as therapeutics with increased selectivity and reduced susceptibility to the resistance mechanisms of tumour cells and infectious pathogens. In this review, we highlight recent advances in defensin research with a particular focus on membrane lipid-targeting in cancer and infection settings. In doing so, we discuss strategies to harness lipid-binding defensins for anticancer and anti-infective therapies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Defensins; Lipids
PubMed: 35015081
DOI: 10.1042/BST20200884 -
Biomedica : Revista Del Instituto... Mar 2021It is essential to determine the interactions between viruses and mosquitoes to diminish dengue viral transmission. These interactions constitute a very complex system...
INTRODUCTION
It is essential to determine the interactions between viruses and mosquitoes to diminish dengue viral transmission. These interactions constitute a very complex system of highly regulated pathways known as the innate immune system of the mosquito, which produces antimicrobial peptides that act as effector molecules against bacterial and fungal infections. There is less information about such effects on virus infections.
OBJECTIVE
To determine the expression of two antimicrobial peptide genes, defensin A and cecropin A, in Aedes aegypti mosquitoes infected with DENV-1.
MATERIALS AND METHODS
We used the F1 generation of mosquitoes orally infected with DENV-1 and real-time PCR analysis to determine whether the defensin A and cecropin A genes played a role in controlling DENV-1 replication in Ae. aegypti. As a reference, we conducted similar experiments with the bacteria Escherichia coli.
RESULTS
Basal levels of defensin A and cecropin A mRNA were expressed in uninfected mosquitoes at different times post-blood feeding. The infected mosquitoes experienced reduced expression of these mRNA by at least eightfold when compared to uninfected control mosquitoes at all times post-infection. In contrast with the behavior of DENV-1, results showed that bacterial infection produced up-regulation of defensin and cecropin genes; however, the induction of transcripts occurred at later times (15 days).
CONCLUSION
DENV-1 virus inhibited the expression of defensin A and cecropin A genes in a wild Ae. aegypti population from Venezuela.
Topics: Aedes; Animals; Antimicrobial Cationic Peptides; Defensins; Dengue Virus
PubMed: 33761199
DOI: 10.7705/biomedica.5491 -
BMC Immunology Nov 2022Macrophages are mononuclear CD34 antigen-presenting cells of defense mechanism and play dual roles in tumor burden. The immunomodulatory and their antitumor function of...
BACKGROUND
Macrophages are mononuclear CD34 antigen-presenting cells of defense mechanism and play dual roles in tumor burden. The immunomodulatory and their antitumor function of β-defensin 2 is still unclear, despite the accumulating evidence of the response in infection. So, the aim of present study is to elucidate the role of β-defensin 2 on the level of ROS, cytokines, chemokine expression in macrophages and antitumor function in breast cancer.
METHOD
Swiss albino mice were used to harvest PEC macrophages and C127i breast cancer cells line for tumor model was used in this study. Macrophages were harvested and characterized by flow-cytometry using F4/80 and CD11c antibodies. MTT was performed to estimate cytotoxicity and dose optimization of β-defensin 2. Oxidative stress was analyzed by HO and NO estimation followed by iNOS quantified by q-PCR. Cytokines and chemokines estimation was done using q-PCR. Co-culture experiment was performed to study anti-tumor function using PI for cell cycle, Annexin -V and CFSE analysis for cell proliferation.
RESULTS
PEC harvested macrophages were characterized by flow-cytometry using F4/80 and CD11c antibodies with the purity of 8% pure population of macrophages. It was found that 99% of cells viable at the maximum dose of 100 ng/ml of β-defensin 2 in MTT. Levels of NO and HO were found to be decreased in β-defensin 2 as compared to control. Expression of cytokines of IFN-γ, IL-1α, TNF-α, TGF-βwas found to be increased while IL-3 was decreased in β-defensin 2 group as compared to control. Levels of chemokines CXCL-1, CXCL-5 and CCL5 increased in treated macrophages while CCL24 and CXCL-15 expression decreased. Adhesion receptor (CD32) and fusion receptor (CD204) were decreased in the β-defensin 2 group as compared to control. Anti-tumor experiment was performed using co-culture experiment apoptosis (Annexin-V) was induced, cell cycle arrest in phage and cell proliferation of C127i cells was decreased.
CONCLUSION
This is the first report of β-defensin 2 modulates macrophage immunomodulatory and their antitumor function in breast cancer. β-defensin 2 as a new therapeutic target for immunotherapy as an adjuvant in vaccines.
Topics: Animals; Mice; beta-Defensins; Hydrogen Peroxide; Macrophages; Cytokines; Chemokines; Annexins; Neoplasms
PubMed: 36324077
DOI: 10.1186/s12865-022-00527-y -
Molecules (Basel, Switzerland) Aug 2018In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their... (Review)
Review
In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their complex behaviors occur across a wide range of time scales and have been challenging to portray. Recent advances in nuclear magnetic resonance and molecular dynamics simulations have revealed the importance of the molecular plasticity of AMPs and their abilities to recognize targets. We also highlight experimental data obtained using nuclear magnetic resonance methodologies, showing that conformational selection is a major mechanism of target interaction in AMP families.
Topics: Animals; Anti-Infective Agents; Defensins; Drug Discovery; Humans; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Peptides; Protein Conformation
PubMed: 30111717
DOI: 10.3390/molecules23082040 -
Viruses Jun 2021Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome...
Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly abundant innate immune factors in neutrophils and epithelial cells, including intestinal Paneth cells, and exhibit antimicrobial and immune-modulatory activities. In this study, we investigated the effects of human α- and β-defensins and RC101, a θ-defensin analog, on SARS-CoV-2 infection. We found that human neutrophil peptides (HNPs) 1-3, human defensin (HD) 5 and RC101 exhibited potent antiviral activity against pseudotyped viruses expressing SARS-CoV-2 spike proteins. HNP4 and HD6 had weak anti-SARS-CoV-2 activity, whereas human β-defensins (HBD2, HBD5 and HBD6) had no effect. HNP1, HD5 and RC101 also inhibited infection by replication-competent SARS-CoV-2 viruses and SARS-CoV-2 variants. Pretreatment of cells with HNP1, HD5 or RC101 provided some protection against viral infection. These defensins did not have an effect when provided post-infection, indicating their effect was directed towards viral entry. Indeed, HNP1 inhibited viral fusion but not the binding of the spike receptor-binding domain to hACE2. The anti-SARS-CoV-2 effect of defensins was influenced by the structure of the peptides, as linear unstructured forms of HNP1 and HD5 lost their antiviral function. Pro-HD5, the precursor of HD5, did not block infection by SARS-CoV-2. High virus titers overcame the effect of low levels of HNP1, indicating that defensins act on the virion. HNP1, HD5 and RC101 also blocked viral infection of intestinal and lung epithelial cells. The protective effects of defensins reported here suggest that they may be useful additives to the antivirus arsenal and should be thoroughly studied.
Topics: A549 Cells; Caco-2 Cells; Defensins; Epithelial Cells; HEK293 Cells; HeLa Cells; Humans; SARS-CoV-2; Virus Internalization
PubMed: 34206990
DOI: 10.3390/v13071246 -
The Biochemical Journal Jan 2019The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific,... (Review)
Review
The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific, and thus might have fewer side effects than traditional small-molecule drugs, is gaining increasing interest among the scientific and in the pharmaceutical industries. Highly constrained macrocyclic polypeptides are exceptionally more stable to chemical, thermal and biological degradation and show better biological activity when compared with their linear counterparts. Many of these relatively new scaffolds have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the disulfide bonds, able to cross cellular membranes and modulate intracellular protein-protein interactions both and These properties make them ideal tools for many biotechnological applications. The present study provides an overview of the new developments on the use of several disulfide-rich backbone-cyclized polypeptides, including cyclotides, θ-defensins and sunflower trypsin inhibitor peptides, in the development of novel bioimaging reagents and therapeutic leads.
Topics: Animals; Cyclization; Cyclotides; Defensins; Disulfides; Humans; Models, Molecular; Molecular Imaging; Peptides, Cyclic
PubMed: 30635453
DOI: 10.1042/BCJ20180792