Anti‐inflammatory and anti‐endotoxin properties of peptides derived from the carboxy‐terminal region of a defensin from the tick <i>Ornithodoros savignyi</i>

Malan, Melissa; Serem, June Cheptoo; Bester, Megan Jean; Neitz, A.W.H.; Gaspar, Anabella R. M.

doi:10.1002/psc.2838

Cited by 20 publications

(22 citation statements)

References 53 publications

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“…Significantly, the hBD3-3 peptide downregulates NF-κB-dependent inflammation and, in a lung inflammation model, reduces interstitial infiltration of polymorphonuclear leukocytes. Os and Os-C are peptides derived also from the carboxy-terminal region, this time of a tick defensin [59]. Both peptides bind E. coli LPS and inhibit LPS/IFN-γ-induced NO and TNF production in murine macrophages identical to those used in the previous paragraph.…”

Section: Pro-and Anti-inflammatory Activitiesmentioning

confidence: 96%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

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Section: Pro-and Anti-inflammatory Activitiesmentioning

confidence: 96%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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“…[10,11] Bioactive peptides are commonly specific fragments of proteins that elicit biological activity and consequently modulate the health status of individuals. Some of the reported bioactivities elicited by bioactive peptides include antibacterial, [13][14][15] antifungal, [16] anti-inflammatory, [17,18] antioxidant, and angiotensin-converting enzyme (ACE) inhibitory activities. This is evident by the propensity of databases and repositories containing huge amount of data on bioactive peptide structure, properties, and activities.…”

Section: Introductionmentioning

confidence: 99%

Structural properties of bioactive peptides with α‐glucosidase inhibitory activity

et al. 2017

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Bioactive peptides are emerging as promising class of drugs that could serve as α-glucosidase inhibitors for the treatment of type 2 diabetes. This article identifies structural and physicochemical requirements for the design of therapeutically relevant α-glucosidase inhibitory peptides. So far, a total of 43 fully sequenced α-glucosidase inhibitory peptides have been reported and 13 of them had IC values several folds lower than acarbose. Analysis of the peptides indicates that the most potent peptides are tri- to hexapeptides with amino acids containing a hydroxyl or basic side chain at the N-terminal. The presence of proline within the chain and alanine or methionine at the C-terminal appears to be relevant for high activity. Hydrophobicity and isoelectric points are less important variables for α-glucosidase inhibition whilst a net charge of 0 or +1 was predicted for the highly active peptides. In silico simulated gastrointestinal digestion revealed that the high and moderately active peptides, including the most potent peptide (STYV), were gastrointestinally unstable, except SQSPA. Molecular docking of SQSPA, STYV, and STY (digestion fragment of STYV) with α-glucosidase suggested that their hydrogen bonding interactions and binding energies were comparable with acarbose. The identified criteria will facilitate the design of new peptide-derived α-glucosidase inhibitors.

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“…At 100 μM Os PMN viability was reduced, but the effect was not statistically significant; however, evaluation of the ultrastructure of these cells showed extensive cellular damage. Malan et al found no toxicity of Os to mouse macrophages (RAW 264.7); however, lower concentrations were used in that study. There may also be differences in toxicity between mouse and human cells as well as cell lines and ex vivo cell populations.…”

Section: Discussionmentioning

confidence: 65%

“…Previous studies indicated that neither synthetic peptide, Os nor Os‐C, were toxic to erythrocytes, fibroblast, epithelial, or macrophage cell lines and possess antioxidant and anti‐inflammatory activity . Phagocytic leukocytes, neutrophils, eosinophils, and basophils play important roles in the innate immune response to pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…Two synthetic antimicrobial peptides, Os and Os‐C (Table ), derived from a tick defensin, have been identified as multifunctional peptides, because of the ability of these peptides to effectively kill bacteria while showing absence of toxicity towards human peripheral erythrocytes and the SC‐1, Caco‐2, and RAW 264.7 cell lines . Both Os and Os‐C bound LPS and inhibited nitric oxide (NO) and TNF‐α production in RAW 264.7 macrophage cells . Os but not Os‐C in this cell line scavenged reactive oxygen species (ROS) and NO.…”

Section: Introductionmentioning

confidence: 99%

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The dual functionality of antimicrobial peptides Os and Os‐C in human leukocytes

Taute

Bester

Gaspar

2019

Journal of Peptide Science

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Antimicrobial peptides (AMPs), Os and Os-C, have been identified as multifunctional peptides with antibacterial, antiendotoxin, and anti-inflammatory properties. For further development of Os and Os-C as therapeutic peptides, it is essential to evaluate these effects in human mononuclear (MN) and polymorphonuclear (PMN) leukocytes. The cytotoxicity and the effects of both peptides on MN and PMN morphology were determined with the Alamar-Blue assay and scanning electron microscopy, respectively. The ability of Os and Os-C to induce reactive oxygen species (ROS) and to protect against 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidative damage in both cell populations was evaluated using 2′,7′-dichlorofluorescin diacetate (DCFH-DA). Using fluorescently labeled peptides, the ability of the peptides to cross the cell membranes of MN and PMN was also evaluated. At the minimum bactericidal concentrations of Os and Os-C, neither peptide was cytotoxic. Os caused morphological features of toxicity at 100 μM, entered MN cells, and also protected these cells against oxidative damage. Os-C caused MN and PMN leukocyte activation associated with ROS formation and was unable to penetrate cell membranes, indicating extracellular membrane interactions.This study confirms that both Os and Os-C at less than 100 μM are not cytotoxic. The MN-specific uptake of Os identifies it as a cellspecific cargo-carrier peptide, with additional anti-inflammatory properties. In contrast, the ability of Os-C to activate MN and PMN cells implies that this peptide should be further evaluated as an AMP, which, in addition to its ability to eradicate infection, can further enhance host immunity. These novel characteristics of Os and Os-C indicate that these AMPs as peptides can be further developed for specific applications.

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Anti‐inflammatory and anti‐endotoxin properties of peptides derived from the carboxy‐terminal region of a defensin from the tick Ornithodoros savignyi

Cited by 20 publications

References 53 publications

Immunomodulatory effects of anti-microbial peptides

Immunomodulatory effects of anti-microbial peptides

Structural properties of bioactive peptides with α‐glucosidase inhibitory activity

The dual functionality of antimicrobial peptides Os and Os‐C in human leukocytes

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