Dataset Information

Inhibitory effect of BMAP-28 on Leptospiral Lipopolysaccharide-Induced TLR2-Dependent Immune Response in Bovine Cells.

ABSTRACT: BACKGROUND:Bovine leptospirosis is a widespread zoonotic disease, leading to serious economic losses in animal production and causing potential hazards to human health. Leptospiral lipopolysaccharide (L-LPS) plays an important role in leptospirosis pathogenicity. OBJECTIVES:With respect to L-LPS endotoxin-like activity, we examined bovine immune response to L-LPS and the inhibitory ability of bovine myeloid antimicrobial peptide-28 (BMAP-28) against L-LPS-induced immune activation in bovine cells. MATERIALS AND METHODS:In this study, L-LPS-induced proinflammatory cytokine production in bovine cells was quantitatively measured with real-time PCR and ELISA, and we determined which cell membrane receptors (toll-like receptor [TLR]2 and TLR4) played a major role. In addition, the ability of BMAP-28 to inhibit L-LPS-induced endotoxin-like immune activation in bovine cells was determined by the decrease in cytokine secretion. RESULTS:L-LPS showed the ability to induce cytokine production in bovine cells, and its induction was TLR2-dependent. BMAP-28 was used to inhibit L-LPS-induced endotoxin-like activity. The function of BMAP-28 was to inhibit LPS-induced TLR2 expression and cytokine production. CONCLUSIONS:In this study, the L-LPS immune response of bovine cells was significant, indicating that TLR2 is the predominant receptor for L-LPS. Due to L-LPS endotoxin-like activity, we found a strategy through using BMAP-28 to prevent L-LPS-induced TLR2-dependent immune activation in bovine cells.

SUBMITTER: Guo Y

PROVIDER: S-EPMC5013549 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Inhibitory effect of BMAP-28 on Leptospiral Lipopolysaccharide-Induced TLR2-Dependent Immune Response in Bovine Cells.

Guo Yijie Y Ding Cuiping C Zhang Bo B Xu Jun J Xun Meng M Xu Jiru J

Jundishapur journal of microbiology 20160621 6

<h4>Background</h4>Bovine leptospirosis is a widespread zoonotic disease, leading to serious economic losses in animal production and causing potential hazards to human health. Leptospiral lipopolysaccharide (L-LPS) plays an important role in leptospirosis pathogenicity.<h4>Objectives</h4>With respect to L-LPS endotoxin-like activity, we examined bovine immune response to L-LPS and the inhibitory ability of bovine myeloid antimicrobial peptide-28 (BMAP-28) against L-LPS-induced immune activation ...[more]

PMID: 27635213

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Project description:Mass treatment with antibiotics at arrival has been the mainstay for bovine respiratory disease (BRD) control but there is an increase in antimicrobial-resistant bacteria being shed from treated cattle. BRD is a disease complex that results from the interaction of viruses or bacteria and susceptible animals with inappropriate immunity. With bacteria being the only feasibly treatable agent and the emergence of antimicrobial resistance, decreased efficacy of commonly used antibiotics could threaten livestock health. There is a need for new antimicrobial alternatives that could be used to control disease. Naturally occurring antimicrobial peptides (AMP) have been proposed to address this need. Here we tested the effect of bovine myeloid antimicrobial peptide-28 (BMAP-28), a synthetic BMAP-28 analog Syn-1, and bactenecin 5 (Bac-5) on Mannheimia haemolytica (Mh) using a quantitative culture method and the broth microdilution method to determine minimum inhibitory and bactericidal concentrations (MIC and MBC). We also tested the antiviral effect of these AMP against bovine herpes-1 (BHV-1) and bovine respiratory syncytial virus (BRSV) using the Reed and Muench method to calculate the viral titers after treatment. We demonstrated that BMAP-28 and Syn-1 can inhibit Mh growth and BMAP-28 can inhibit replication of BHV-1 and BRSV. Moreover, we showed that BMAP-28 and Bac-5 can be used together to inhibit Mh growth. When used alone, the MIC of BMAP-28 and Bac-5 was 64 and 128 μg/mL respectively, but when applied together, their MIC ranged from 0.25-16 for BMAP-28 and 8-64 μg/mL for Bac-5, resulting in a decrease in concentration of up to 256 and 16-fold, respectively. The synergistic interaction between those peptides resulted in concentrations that could be well tolerated by cells. Our results demonstrate that bovine cathelicidins could be used as alternatives to antimicrobials against BRD pathogens. These findings introduce a path to discovering new antimicrobials and determining how these peptides could be tailored to improve cattle health.

Project description:BackgroundProtozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.Methodology/principal findingsAn MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.Conclusions/significanceInterestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials.

Dataset Information

Inhibitory effect of BMAP-28 on Leptospiral Lipopolysaccharide-Induced TLR2-Dependent Immune Response in Bovine Cells.

Publications

Inhibitory effect of BMAP-28 on Leptospiral Lipopolysaccharide-Induced TLR2-Dependent Immune Response in Bovine Cells.

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