Peptide 19-2.5 Inhibits Heparan Sulfate-Triggered Inflammation in Murine Cardiomyocytes Stimulated with Human Sepsis Serum

Märtin, Lukas; Schmitz, Susanne; Santis, Rebecca De; Doemming, Sabine; Haase, Hajo; Hoeger, Janine; Heinbockel, Lena; Brandenburg, Klaus; Marx, Gernot; Schürholz, Tobias

doi:10.1371/journal.pone.0127584

Cited by 36 publications

(73 citation statements)

References 41 publications

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“…Treatment of murine cardiomyocytes stimulated with pathogen-associated or host danger-associated molecular patterns with peptide Pep19-2.5 decreases the inflammatory response [94]. The peptide also blocks a pro-inflammatory response induced by soluble heparan sulfate in serum from patients with gram-negative or gram-positive septic shock.…”

Section: Anti-lipopolysaccharide Peptidementioning

confidence: 99%

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: Anti-lipopolysaccharide Peptidementioning

confidence: 99%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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“…Elimination and reconstitution of HS in serum of septic shock patients were performed as described recently (4). Briefly, HS was eliminated using a biotinconjugated polyclonal antibody against HS (host: rabbit, clone: PAA565Hu71, USCN Life Science Ltd Co., Wuhan, China) and affinity chromatography (Pierce Streptavidin Agarose Columns, Thermo Scientific Inc., Worcester, Massachusetts) according to the manufacturer's instructions.…”

Section: Elimination and Reconstitution Of Hs In Serum Of Septic Shocmentioning

confidence: 99%

“…HL-1 cardiomyocytes were originally purchased from William Claycomb, Louisiana State University (17) and cultured as described recently (4). Briefly, the cells were grown on 5 mg/mL fibronectin and 0.02% gelatin.…”

Section: Cell Culture and Stimulationmentioning

confidence: 99%

“…RNA extraction and PCR were performed as described recently (4). Briefly, total RNA was prepared using TRIzol reagent (Invitrogen, Carlsbad, California).…”

Section: Rna Extraction and Pcrmentioning

confidence: 99%

“…Lipopolysaccharide (LPS) has been proposed as an important circulating myocardial depressant factor; however, myocardial dysfunction is not restricted to gram-negative bacterial sepsis (3). More recently, endogenous danger-associated molecules have been identified to act alike and to intensify inflammatory response (4). Here, heparan sulfate proteoglycans play a key role (5).…”

Section: Introductionmentioning

confidence: 99%

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Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes

Märtin¹,

Peters²,

Schmitz³

et al. 2015

Shock

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The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide-induced mitochondrial dysfunction; however myocardial dysfunction is not restricted to gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared with unstimulated cells (P < 0.0001 and P < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared with unstimulated cells (P = 0.1174 and P = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared with unstimulated cells (P < 0.0001 and P = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared with cells stimulated with HS-free serum (P < 0.0001). Expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) and their co-activators PGC-1α, which regulate mitochondrial function, were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1α mRNA-levels compared with HS-free serum (P = 0.0082, P = 0.0128, and P = 0.0185, respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1α (all P < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting that HS may be targets of therapeutics in septic cardiomyopathy.

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A review on comparative mechanistic studies of antimicrobial peptides against archaea

Varnava

Ronimus

Sarojini

2017

Biotech & Bioengineering

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Archaea was until recently considered as a third domain of life in addition to bacteria and eukarya but recent studies support the existence of only two superphyla (bacteria and archaea). The fundamental differences between archaeal, bacterial, and eukaryal cells are probably the main reasons for the comparatively lower susceptibility of archaeal strains to current antimicrobial agents. The possible emerging pathogenicity of archaea and the role of archaeal methanogens in methane emissions, a potent greenhouse gas, has led many researchers to examine the sensitivity patterns of archaea and make attempts to find agents that have significant anti-archaeal activity. Even though antimicrobial peptides (AMPs) are well known with several published reviews concerning their mode of action against bacteria and eukarya, to our knowledge, to date no reviews are available that focus on the action of these peptides against archaea. Herein, we present a review on all the peptides that have been tested against archaea. In addition, in an attempt to shed more light on possible future work that needs to be performed we have included a brief overview of the chemical characteristics, spectrum of activity, and the known mechanism of action of each of these peptides against bacteria and/or fungi. We also discuss the nature of and key physiological differences between Archaea, Bacteria, and Eukarya that are relevant to the development of anti-archaeal peptides. Despite our relatively limited knowledge about archaea, available data suggest that AMPs have an even broader spectrum of activity than currently recognized.

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Peptide 19-2.5 Inhibits Heparan Sulfate-Triggered Inflammation in Murine Cardiomyocytes Stimulated with Human Sepsis Serum

Cited by 36 publications

References 41 publications

Immunomodulatory effects of anti-microbial peptides

Immunomodulatory effects of anti-microbial peptides

Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes

A review on comparative mechanistic studies of antimicrobial peptides against archaea

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