The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates

Hansen, Bjoern-Thore; Maschkowitz, Gregor; Podschun, Rainer; Fickenscher, Helmut

doi:10.3389/fmicb.2021.757215

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Notably, neutrophils express the IL-26 receptor complex (IL-10R2/IL-20R1) (21), and stimulation of human neutrophils with IL-26 ex vivo enhances their chemotactic response to IL-8 and fMLP, an archetype chemokine and a pathogenically relevant bacterial component, respectively (21), while at the same time inhibiting the non-specific release of neutrophil elastase and myeloperoxidase, two potentially selfdamaging enzymes (24). In addition, we have demonstrated the involvement of IL-26 in human bacterial pneumonia (24) and provided confirming evidence that IL-26 exerts direct antibacterial effects, resembling those of an antimicrobial peptide, thereby forwarding IL-26 as a kinocidin (24)(25)(26).…”

Section: Introductionsupporting

confidence: 58%

TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26

et al. 2023

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BackgroundBacterial infection causes accumulation of neutrophils that release antimicrobial proteins including heparin-binding protein (HBP). In human airways, this neutrophil accumulation can be re-capitulated via intrabronchial exposure to lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, that also causes a local increase in the neutrophil-mobilizing cytokine IL-26. Although LPS is considered a weak stimulus for HBP release ex vivo, its effect on HBP release in human airways in vivo has not been characterized.MethodsWe determined whether intrabronchial exposure to LPS causes concomitant release of HBP and IL-26 in human airways, and whether IL-26 can enhance LPS-induced release of HBP in isolated human neutrophils. ResultsWe found that the concentration of HBP was markedly increased in bronchoalveolar lavage (BAL) fluid 12, 24, and 48 hours after LPS exposure, and that it displayed a strong and positive correlation with that of IL-26. Moreover, the concentration of HBP in conditioned media from isolated neutrophils was enhanced only after co-stimulation with LPS and IL-26.ConclusionsTaken together, our findings indicate that TLR4 stimulation causes concomitant release of HBP and IL-26 in human airways, and that IL-26 may constitute a required co-stimulant for HBP release in neutrophils, thus enabling the concerted action of HBP and IL-26 in local host defense.

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Section: Introductionsupporting

confidence: 58%

TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26

et al. 2023

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“…Susceptibility testing: Killing rates of different concentrations of tetrapods and amorphous s-ZnO particles against Gram-negative and Gram-positive bacteria were determined as described previously [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Antibacterial Activity of Nanostructured Zinc Oxide Tetrapods

Büter

Maschkowitz

Baum

et al. 2023

IJMS

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Zinc oxide (ZnO) tetrapods as microparticles with nanostructured surfaces show peculiar physical properties and anti-infective activities. The aim of this study was to investigate the antibacterial and bactericidal properties of ZnO tetrapods in comparison to spherical, unstructured ZnO particles. Additionally, killing rates of either methylene blue-treated or untreated tetrapods and spherical ZnO particles for Gram-negative and Gram-positive bacteria species were determined. ZnO tetrapods showed considerable bactericidal activity against Staphylococcus aureus, and Klebsiella pneumoniae isolates, including multi-resistant strains, while Pseudomonas aeruginosa and Enterococcus faecalis remained unaffected. Almost complete elimination was reached after 24 h for Staphylococcus aureus at 0.5 mg/mL and Klebsiella pneumoniae at 0.25 mg/mL. Surface modifications of spherical ZnO particles by treatment with methylene blue even improved the antibacterial activity against Staphylococcus aureus. Nanostructured surfaces of ZnO particles provide active and modifiable interfaces for the contact with and killing of bacteria. The application of solid state chemistry, i.e., the direct matter-to-matter interaction between active agent and bacterium, in the form of ZnO tetrapods and non-soluble ZnO particles, can add an additional principle to the spectrum of antibacterial mechanisms, which is, in contrast to soluble antibiotics, depending on the direct local contact with the microorganisms on tissue or material surfaces.

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“…As shown by Hansen et al, IL-26 demonstrates strong bactericidal activities against E. faecalis, S. aureus, and Acinetobacter baumannii, weak fungicidal effect against C. albicans and inhibits the replication of cytomegalovirus and hepatitis C virus. [18] In addition to a high isoelectric point, the positively charged amphipathic helices E and F (and part of helix C) confer not only bacterial membrane puncturing properties but also DNAbinding properties upon IL-26. This (IFN-γ) interferons, which orchestrate innate antiviral responses.…”

Section: Kinocidins (Chemokines Interleukins Interferons)mentioning

confidence: 99%

“…Although there are numerous interleukin‐type cytokines, IL‐26 is one of the few to exhibit kinocidin properties (Figure 3). [18] IL‐26 is a member of the IL‐20 cytokine subfamily which in turn is a member of the IL‐10 family. IL‐26, encoded by the IL‐26 gene on chromosome 12 (12q15), is a 171‐amino acid protein with a secondary structure dominated by six α‐helices (A−F).…”

Section: Six Molecular Classes Of Eaimsmentioning

confidence: 99%

“…These amphipathic α‐helices allow IL‐26 to function as a cationic cell‐penetrating peptide with the same cytotoxic antimicrobial properties as an AMP. As shown by Hansen et al ., IL‐26 demonstrates strong bactericidal activities against E. faecalis, S. aureus , and Acinetobacter baumannii , weak fungicidal effect against C. albicans and inhibits the replication of cytomegalovirus and hepatitis C virus [18] …”

Section: Six Molecular Classes Of Eaimsmentioning

confidence: 99%

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Endogenous Antimicrobial‐Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity

Weaver

2024

ChemBioChem

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Endogenous antimicrobial‐immunomodulatory molecules (EAIMs) are essential to immune‐mediated human health and evolution. Conventionally, antimicrobial peptides (AMPs) have been regarded as the dominant endogenous antimicrobial molecule; however, AMPs are not sufficient to account for the full spectrum of antimicrobial‐immunomodulatory duality occurring within the human body. The threat posed by pathogenic microbes is pervasive with the capacity for widespread impact across many organ systems and multiple biochemical pathways; accordingly, the host needs the capacity to react with an equally diverse response. This can be attained by having EAIMs that traverse the full range of molecular size (small to large molecules) and structural diversity (including molecules other than peptides). This review identifies multiple molecules (peptide/protein, lipid, carbohydrate, nucleic acid, small organic molecule, and metallic cation) as EAIMs and discusses the possibility of cooperative, additive effects amongst the various EAIM classes during the host response to a microbial assault. This comprehensive consideration of the full molecular diversity of EAIMs enables the conclusion that EAIMs constitute a previously uncatalogued structurally diverse and collectively underappreciated immuno‐active group of integrated molecular responders within the innate immune system’s first line of defence.

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The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates

Cited by 8 publications

References 32 publications

TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26

TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26

Antibacterial Activity of Nanostructured Zinc Oxide Tetrapods

Endogenous Antimicrobial‐Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity

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