The Antibacterial and Anti-inflammatory Activity of Chicken Cathelicidin-2 combined with Exogenous Surfactant for the Treatment of Cystic Fibrosis-Associated Pathogens

Banaschewski, Brandon John Harrison; Baer, Brandon; Arsenault, Christina; Jazey, Teah; Veldhuizen, Edwin J.A.; Delport, Johan; Gooyers, Tracey; Lewis, James F.; Haagsman, Henk P.; Veldhuizen, Ruud A. W.; Yamashita, Cory

doi:10.1038/s41598-017-15558-4

Cited by 20 publications

(13 citation statements)

References 64 publications

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“…Furthermore, our recombinant hybrid peptide depicted high immunomodulatory and anti-inflammatory activities, and also neutralized the bioactivity of endotoxin without cytotoxic and hemolytic effects as modeled in Figure 6. These data are in agreement with the previous study reporting high antiinflammatory and LPS neutralizing activity of CATH-2 without hemolytic activity (van Dijk et al, 2016;Banaschewski et al, 2017). Moreover, endotoxin up-regulates adhesion molecules (Lush et al, 2000) and induces apoptosis (Bannerman and Goldblum, 2003).…”

Section: Discussionsupporting

confidence: 93%

In vitro Impact of Yeast Expressed Hybrid Peptide CATH-2TP5 as a Prophylactic Measure Toward Sepsis and Inflammation

Ahmad

Hanif

Xin

et al. 2020

Front. Bioeng. Biotechnol.

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CATH-2TP5 is a linear cationic hybrid peptide, consequent from naturally occurring antimicrobial peptide (AMPs) Cathelicidin-2 (CATH-2) and Immunomodulatory peptide Thymopentin (TP5) having dynamic and potent anti-inflammatory activities without hemolytic effect. The biocompatible mechanism of CATH-2TP5 is favored to explore new methodologies in the direction of biomedical applications. In this retrospectively study, an antiendotoxin and anti-inflammatory hybrid peptide CATH-2TP5 was emulated into pPICZα-A and successfully expressed in Pichia pastoris (P. pastoris). The recombinant CATH-2TP5 was purified through the Ni-affinity column and reversedphase HPLC. The purified CATH-2TP5 peptide exhibited robust anti-endotoxin activity and significantly (p < 0.05) neutralized the effect of lipopolysaccharide (LPS). Furthermore, the down-regulated effect of CATH-2TP was more pronounced (p < 0.05) on LPS-induced cytotoxic effects, nitric oxide secretion and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in murine RAW264.7 macrophages. As associated to control and parental peptide the number of apoptotic cells was also contracted with the treatment of CATH-2TP5. Thus, we concluded that CATH-2TP5 peptide may be used in various biomedical applications as a therapeutic drug.

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Section: Discussionsupporting

confidence: 93%

In vitro Impact of Yeast Expressed Hybrid Peptide CATH-2TP5 as a Prophylactic Measure Toward Sepsis and Inflammation

Ahmad

Hanif

Xin

et al. 2020

Front. Bioeng. Biotechnol.

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“…Animals were monitored for 6 h following instillation, before being euthanized by intraperitoneal injection of sodium pentobarbital and exsanguination, by severing the descending aorta. After this, a bronchoalveolar lavage (BAL) was performed as previously described [ 16 ], before the lungs were excised, divided into four pieces and snap frozen in liquid nitrogen to be stored at – 80 °C.…”

Section: Methodsmentioning

confidence: 99%

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer

McCaig

Yamashita

et al. 2020

Lung

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Background Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery. To improve the pulmonary distribution of glucocorticoids, such as budesonide to distal regions of the lung, exogenous surfactant has been proposed as an ideal delivery vehicle for such therapies. It was therefore hypothesized that fortifying an exogenous surfactant (BLES) with budesonide would enhance efficacy for treating pulmonary inflammation in vivo. Methods An intratracheal instillation of heat-killed bacteria was used to elicit an inflammatory response in the lungs of male and female rats. Thirty minutes after this initial instillation, either budesonide or BLES combined with budesonide was administered intratracheally. To evaluate the efficacy of surfactant delivery, various markers of inflammation were measured in the bronchoalveolar lavage and lung tissue. Results Although budesonide exhibited anti-inflammatory effects when administered alone, delivery with BLES enhanced those effects by lowering the lavage neutrophil counts and myeloperoxidase activity in lung tissue. Combining budesonide with BLES was also shown to reduce several other pro-inflammatory mediators. These results were shown across both sexes, with no observed sex differences. Conclusion Based on these findings, it was concluded that exogenous surfactant can enhance the delivery and efficacy of budesonide in vivo.

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“…In an effort to separate these effects, several studies have now used different types of inactivated bacteria to investigate the direct anti-inflammatory role of cathelicidins in vivo. For instance, inflammatory responses induced by intratracheal administration of heat-inactivated P. aeruginosa or S. aureus isolates in mice can be inhibited by coadministration or post-administration of chicken CATH-2 (73,165). In addition, intratracheal administration of chicken CATH-2-killed P. aeruginosa induces less neutrophil influx and inflammatory cytokine production compared to either administration of heat-killed or gentamicin-killed P. aeruginosa (73).…”

Section: Cathelicidin-mediated Tlr Modulation In Vivomentioning

confidence: 99%

Cathelicidins Modulate TLR-Activation and Inflammation

et al. 2020

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Cathelicidins are short cationic peptides that are part of the innate immune system. At first, these peptides were studied mostly for their direct antimicrobial killing capacity, but nowadays they are more and more appreciated for their immunomodulatory functions. In this review, we will provide a comprehensive overview of the various effects cathelicidins have on the detection of damage-and microbe-associated molecular patterns, with a special focus on their effects on Toll-like receptor (TLR) activation. We review the available literature based on TLR ligand types, which can roughly be divided into lipidic ligands, such as LPS and lipoproteins, and nucleic-acid ligands, such as RNA and DNA. For both ligand types, we describe how direct cathelicidin-ligand interactions influence TLR activation, by for instance altering ligand stability, cellular uptake and receptor interaction. In addition, we will review the more indirect mechanisms by which cathelicidins affect downstream TLR-signaling. To place all this information in a broader context, we discuss how these cathelicidin-mediated effects can have an impact on how the host responds to infectious organisms as well as how these effects play a role in the exacerbation of inflammation in auto-immune diseases. Finally, we discuss how these immunomodulatory activities can be exploited in vaccine development and cancer therapies.

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The Antibacterial and Anti-inflammatory Activity of Chicken Cathelicidin-2 combined with Exogenous Surfactant for the Treatment of Cystic Fibrosis-Associated Pathogens

Cited by 20 publications

References 64 publications

In vitro Impact of Yeast Expressed Hybrid Peptide CATH-2TP5 as a Prophylactic Measure Toward Sepsis and Inflammation

In vitro Impact of Yeast Expressed Hybrid Peptide CATH-2TP5 as a Prophylactic Measure Toward Sepsis and Inflammation

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Cathelicidins Modulate TLR-Activation and Inflammation

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