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Schinus terebinthifolia leaf lectin (SteLL) is an immunomodulatory agent by altering cytokine release by mice splenocytes.

ABSTRACT: Schinus terebinthifolia leaf lectin (SteLL) was reported to be an antimicrobial and antitumor agent. In this work, we evaluated the immunomodulatory activity of SteLL on mice splenocytes and also determined its native molecular mass and putative sequence similarities with plant proteins. The effects of SteLL (12.5 μg/mL) on viability, cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt), cytosolic and mitochondrial levels of reactive oxygen species (ROS), and mitochondrial transmembrane potential (ΔΨm) of mice splenocytes were determined. In addition, the culture supernatants were collected for quantification of interleukins (IL), tumor necrosis factor (TNF), interferon-gamma (IFN-γ) and nitric oxide (NO). SteLL showed a native molecular mass of 12.4 kDa and tandem mass spectrometry (MS/MS) ions search revealed similarities with adenosine triphosphate (ATP) synthase and F1-ATPase from plants (4% and 6% coverage, respectively). SteLL was not toxic to splenocytes, did not alter the [Ca²⁺]_cyt and ROS levels, and slightly reduced ΔΨm. The presence of SteLL stimulated the cells to release pro-inflammatory cytokines (IL-17A, TNF-α, IFN-γ and IL-2) and also of IL-4, an anti-inflammatory cytokine that can prevent exacerbated inflammation. SteLL induced decrease in the secretion of NO. In conclusion, SteLL has biotechnological potential as an immunomodulator agent for use in studies employing cultures of immune cells. In addition, the anti-infectious and antitumor properties of the leaves may involve the immunomodulation property of SteLL.

SUBMITTER: Dos Santos AJCA

PROVIDER: S-EPMC7052083 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Schinus terebinthifolia leaf lectin (SteLL) has anti-infective action and modulates the response of Staphylococcus aureus-infected macrophages.

Project description:Staphylococcus aureus is recognized as an important pathogen causing a wide spectrum of diseases. Here we examined the antimicrobial effects of the lectin isolated from leaves of Schinus terebinthifolia Raddi (SteLL) against S. aureus using in vitro assays and an infection model based on Galleria mellonella larvae. The actions of SteLL on mice macrophages and S. aureus-infected macrophages were also evaluated. SteLL at 16?µg/mL (8?×?MIC) increased cell mass and DNA content of S. aureus in relation to untreated bacteria, suggesting that SteLL impairs cell division. Unlike ciprofloxacin, SteLL did not induce the expression of recA, crucial for DNA repair through SOS response. The antimicrobial action of SteLL was partially inhibited by 50 mM N-acetylglucosamine. SteLL reduced staphyloxathin production and increased ciprofloxacin activity towards S. aureus. This lectin also improved the survival of G. mellonella larvae infected with S. aureus. Furthermore, SteLL induced the release of cytokines (IL-6, IL-10, IL-17A, and TNF-?), nitric oxide and superoxide anion by macrophagens. The lectin improved the bactericidal action of macrophages towards S. aureus; while the expression of IL-17A and IFN-? was downregulated in infected macrophages. These evidences suggest SteLL as important lead molecule in the development of anti-infective agents against S. aureus.

| S-EPMC6890730 | biostudies-literature

Sewage sludge as substrate in Schinus terebinthifolia raddi seedlings commercial production.

Project description:Schinus terebinthifolia Raddi is a species with several potential uses; selecting the proper substrate and fertilizer rate can be vital for seedling production in a nursery environment. This study aims to evaluate two substrates, namely: (i) sewage sludge (SS) from Ilha WWTP; (ii) a commercial substrate (CS) made of organic materials (mainly sphagnum peat). Increasing rates of controlled-release fertilizer - CRF (0, 3, 6, and 12 kg m-3) were applied. The experiment was completely randomized with a factorial 2 × 4 scheme (substrates × rates). The seedlings' growth, biomass, and quality were evaluated. The treatments were compared by Tukey test and regression analysis, where linear, quadratic, and cubic models were considered. Principal components analysis (PCA) and cluster analysis were performed. The CRF rates showed non-significant effects for most of the investigated variables in the SS substrate. In the CS, a 7.8 kg m-3 rate of CRF showed the best growth performance. The multivariate analysis of the morphological parameters proved suitable as a complementary approach to evaluate the seedlings' quality. Seedlings reached recommended values for height, diameter, and quality in the 100% SS substrate without chemical fertilizers; thus, Schinus terebinthifolia production in the SS from Ilha is recommended. Besides the growth advantage, the SS can promote nursery cost savings with commercial substrates and chemical fertilizers.

| S-EPMC9568525 | biostudies-literature

Pentagalloyl glucose from Schinus terebinthifolia inhibits growth of carbapenem-resistant Acinetobacter baumannii.

Project description:The rise of antibiotic resistance has necessitated a search for new antimicrobials with potent activity against multidrug-resistant gram-negative pathogens, such as carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, a library of botanical extracts generated from plants used to treat infections in traditional medicine was screened for growth inhibition of CRAB. A crude extract of Schinus terebinthifolia leaves exhibited 80% inhibition at 256 µg/mL and underwent bioassay-guided fractionation, leading to the isolation of pentagalloyl glucose (PGG), a bioactive gallotannin. PGG inhibited growth of both CRAB and susceptible A. baumannii (MIC 64-256 µg/mL), and also exhibited activity against Pseudomonas aeruginosa (MIC 16 µg/mL) and Staphylococcus aureus (MIC 64 µg/mL). A mammalian cytotoxicity assay with human keratinocytes (HaCaTs) yielded an IC50 for PGG of 256 µg/mL. Mechanistic experiments revealed iron chelation as a possible mode of action for PGG's activity against CRAB. Passaging assays for resistance did not produce any resistant mutants over a period of 21 days. In conclusion, PGG exhibits antimicrobial activity against CRAB, but due to known pharmacological restrictions in delivery, translation as a therapeutic may be limited to topical applications such as wound rinses and dressings.

| S-EPMC7501240 | biostudies-literature

Triterpenoid acids isolated from Schinus terebinthifolia fruits reduce Staphylococcus aureus virulence and abate dermonecrosis.

Project description:Staphylococcus aureus relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of "430D-F5", a refined extract derived from the fruits of Schinus terebinthifolia, a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid (1), 3-oxotirucalla-7,24Z-dien-26-oic acid (2) and 3?-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC50 2-70??M). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC50 0.4-25??M) and glycerol ester hydrolase or lipase (gehB, IC50 1.5-25??M). Surprisingly, dose-dependent activity against the nuclease reporter (nuc), which is under the control of the sae two-component system, was also observed (IC50 0.4-12.5??M). Compounds 1-3 exhibited little to no effect on the agr-independent mgrA P2 reporter (a constitutive promoter from the mgrA two-component system) and the esxA reporter (under control of mgrA). Compounds 1-3 inhibited ?-toxin production in vitro and reduced dermonecrosis in a murine in vivo model. This is the first report of triterpenoid acids with potent anti-virulence effects against S. aureus.

| S-EPMC7229044 | biostudies-literature

Uncovering the phylogeography of <i>Schinus terebinthifolia</i> in South Africa to guide biological control.

Project description:Schinus terebinthifolia is a problematic invasive alien plant (IAP) in South Africa that is a high priority target for biological control. Biological control has been implemented in the states of Florida and Hawaii (USA), where S. terebinthifolia is also an IAP. Phylogeographic work determined that there have been multiple introductions of two lineages (haplotype A and B) into the USA. Haplotype A was introduced to western Florida and Hawaii, while haplotype B was introduced to eastern Florida. Haplotypes A and B have subsequently hybridized in Florida, resulting in novel plant genotypes. Biological control agents in the USA are known to vary in efficacies on the two different haplotypes and hybrids. This study used molecular techniques to uncover the source populations of S. terebinthifolia in South Africa using chloroplast DNA and microsatellites. Populations from the introduced ranges in Florida (east, west and hybrids) and Hawaii were included (n = 95). All South Africa populations (n = 51) were found to be haplotype A. Microsatellite analysis determined shared alleles with western Florida and Hawaiian populations. The likely source of South African S. terebinthifolia was determined to be western Florida through the horticultural trade. These results will help guide a biological control programme to source agents that perform well on these populations in the USA. Furthermore, the presence of only one haplotype in South Africa highlights the need to ensure no further introductions of other haplotypes of the plant are made, in order to avoid similar hybridization events like those recorded in Florida.

| S-EPMC8783615 | biostudies-literature

Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy-induced cytokine release syndrome.

Project description:Objectives:Humanised mice have emerged as valuable models for pre-clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft-versus-host disease (GvHD). Methods:To overcome donor-induced variation, we directly compared the in vitro and in vivo immune phenotype of immunodeficient NSG mice reconstituted with human bone marrow (BM) CD34+ haematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs) or spleen mononuclear cells (SPMCs) from the same human donors. SPMC engraftment in NSG-dKO mice, which lack MHC class I and II, was also evaluated as a strategy to limit GvHD. Another group of mice was engrafted with umbilical cord blood (UCB) CD34+ HSCs. Induction of CRS in vivo was investigated upon administration of the anti-CD3 monoclonal antibody OKT3. Results:PBMC- and SPMC-reconstituted NSG mice showed short-term survival, with engrafted human T cells exhibiting mostly an effector memory phenotype. Survival in SPMC-reconstituted NSG-dKO mice was significantly longer. Conversely, both BM and UCB-HSC models showed longer survival, without demonstrable GvHD and a more naïve T-cell phenotype. PBMC- and SPMC-reconstituted mice, but not BM-HSC or UCB-HSC mice, experienced severe clinical signs of CRS upon administration of OKT3. Conclusion:PBMC- and SPMC-reconstituted NSG mice better predict OKT3-mediated CRS. The SPMC model allows generation of large experimental groups, and the use of NSG-dKO mice mitigates the limitation of early GvHD.

| S-EPMC7641894 | biostudies-literature

An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions.

Project description:Cytotoxic therapeutic monoclonal antibodies (mAbs) often mediate target cell-killing by eliciting immune effector functions via Fc region interactions with cellular and humoral components of the immune system. Key functions include antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). However, there has been increased appreciation that along with cell-killing functions, the induction of antibody-dependent cytokine release (ADCR) can also influence disease microenvironments and therapeutic outcomes. Historically, most Fc engineering approaches have been aimed toward modulating ADCC, ADCP, or CDC. In the present study, we describe an Fc engineering approach that, while not resulting in impaired ADCC or ADCP, profoundly affects ADCR. As such, when peripheral blood mononuclear cells are used as effector cells against mAb-opsonized tumor cells, the described mAb variants elicit a similar profile and quantity of cytokines as IgG1. In contrast, although the variants elicit similar levels of tumor cell-killing as IgG1 with macrophage effector cells, the variants do not elicit macrophage-mediated ADCR against mAb-opsonized tumor cells. This study demonstrates that Fc engineering approaches can be employed to uncouple macrophage-mediated phagocytic and subsequent cell-killing functions from cytokine release.

| S-EPMC4622058 | biostudies-literature

In-vitro validation of cytokine neutralizing antibodies by testing with ovine mononuclear splenocytes.

Project description:Cytokines have gained increasing attention as therapeutic targets in inflammation-related disorders and inflammatory conditions have been investigated in sheep. Monoclonal antibodies (mAbs) specific for the ovine pro-inflammatory cytokines interleukin (IL)-1? and IL-6 could be used to study the effects of blocking pro-inflammatory cytokines in sheep. Ovine-specific IL-1? and IL-6 proteins and mAbs specific for these molecules were produced and the ability of the mAbs to neutralize the proteins was tested in cultures of ovine splenic mononuclear cells. Expression of nuclear factor (NF)-?? and signal transducer and activator of transcription (STAT)-3 was evaluated by western blotting and densitometric quantification. Treatment with purified IL-1? and IL-6 proteins increased NF-?? (P < 0.001) and STAT-3 (P < 0.01) expression, respectively, in cell culture. Treatment with these proteins that were pre-incubated with IL-1? and IL-6 mAbs attenuated (P < 0.01) these effects. These results confirm the bioactivity of ovine IL-1? and IL-6 proteins and the neutralizing capacity of anti-ovine-IL-1? and -IL-6 mAbs in vitro. These mAbs could be used to investigate anti-inflammatory strategies for attenuation of the effects of these pro-inflammatory cytokines in sheep.

| S-EPMC3481012 | biostudies-literature

Systemic effects in naive mice injected with immunomodulatory lectin ArtinM.

Project description:Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 ?g) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 ?g), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 ?g). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ?2.5 ?g. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-?, TNF-?, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 ?g ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-?t were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

| S-EPMC5662225 | biostudies-literature

Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes.

Project description:Infections with Pseudomonas aeruginosa may cause many different diseases. The spectrum of such infections in general includes inflammation and bacterial sepsis. Hospital-acquired pneumonia, naturally resistant to a wide range of antibiotics, is associated with a particularly high mortality rate in mechanically ventilated patients. The pathogenesis of P. aeruginosa is complex and mediated by several virulence factors, as well as cell-associated factors. We have previously demonstrated that stimulation with different bacteria triggers the cytokine response of thymocytes. In this study, we investigated the effect of P. aeruginosa and its different components on the cytokine production of immature and mature immune cells. We found that the induced cytokine pattern in the thymus and the spleen after infections with P. aeruginosa is primarily mediated by lipopolysaccharide (LPS) of the outer cell membrane, but other components of the bacterium can influence the cytokine secretion as well. Stimulation with heat-killed P. aeruginosa and LPS does not influence the amount of cytokine-producing CD4(+) T cells but instead suppresses the emergence of Th17 cells. However, stimulation with P. aeruginosa or its components triggers the interleukin-17 (IL-17) response both in thymocytes and in splenocytes. We conclude that infections with P. aeruginosa affect the cytokine secretion of immature and mature cells and that IL-17 and Th17 cells play only a minor role in the development of pathological systemic inflammatory disease conditions during P. aeruginosa infections. Therefore, other inflammatory immune responses must be responsible for septic reactions of the host.

| S-EPMC4862705 | biostudies-other

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