IL-22 Induces an Acute-Phase Response Associated to a Cohort of Acute Phase Proteins and Antimicrobial Peptides as Players of Homeostasis

Veas, Francisco; Dubois, Gérard

doi:10.5772/20386

Cited by 3 publications

(3 citation statements)

References 78 publications

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“…Due to their cationic nature, most AMPs preferentially interact with negatively charged membranes, such as those of bacteria. The presence of cholesterol and the absence of acidic phospholipids in normal human cell membranes are at the basis of AMPs’ selective toxicity toward prokaryotic cells . Conversely, the net negative charge of tumoral cell membranes, conferred by modifications in phospholipid composition, promotes the anticancer activity of some AMPs. − When incubated with normal human fibroblasts, ApoB-derived encrypted peptides exhibited mild toxicity (up to 20–30% decrease in cell viability) after 72 h of peptide treatment at 20 μmol L –1 .…”

Section: Results and Discussionmentioning

confidence: 99%

Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma

et al. 2022

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Encrypted peptides have been recently found in the human proteome and represent a potential class of antibiotics. Here we report three peptides derived from the human apolipoprotein B (residues 887−922) that exhibited potent antimicrobial activity against drug-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococci both in vitro and in an animal model. The peptides had excellent cytotoxicity profiles, targeted bacteria by depolarizing and permeabilizing their cytoplasmic membrane, inhibited biofilms, and displayed anti-inflammatory properties. Importantly, the peptides, when used in combination, potentiated the activity of conventional antibiotics against bacteria and did not select for bacterial resistance. To ensure translatability of these molecules, a protease resistant retro-inverso variant of the lead encrypted peptide was synthesized and demonstrated anti-infective activity in a preclinical mouse model. Our results provide a link between human plasma and innate immunity and point to the blood as a source of much-needed antimicrobials.

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Section: Results and Discussionmentioning

confidence: 99%

Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma

et al. 2022

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“…IL-22 induces an acute phase response with up-regulation of acute phase proteins including CRP. 25,26 Accordingly, a subset…”

Section: Pharmacokinetics and Safety Of Rhil-22 Administration In Pat...mentioning

confidence: 99%

A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract

Ponce

Alousi

Nakamura

et al. 2023

Blood

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Graft vs. host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, Interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating safety and efficacy of a novel recombinant human Interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD (NCT02406651; https://clinicaltrials.gov/ct2/show/NCT02406651). The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. 19/27 patients (70%; 80% CI: 56-79) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This work was supported by funding from Evive Biotech., The Society of Memorial Sloan Kettering Cancer Center, and the National Institutes of Health.

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“…In order to use CCO cells in bioassays, IL22Rα1 expression in these cells was confirmed using gene expression analysis (supporting material Figure S7). As a measure of mammalian IL-22 activity, upregulation in the expression of select response genes linked with antimicrobial activity and tissue repair function are typically monitored (Veas andDubois, 2011, Wozniak, Hole, Yano, Fidel, &Wormley, 2014). Three response genes in cfIL-22 treated CCO cells were identified and assessed as a measure of cfIL-22 function: Fibronectin, for assessing tissue repair; interferon, a general immune response protein; and natural killer Lysin-1 an antimicrobial peptide involved in directly killing invading bacteria.…”

Section: Gene Expression Analysismentioning

confidence: 99%

Plant Production and Functional Characterization of Catfish Interleukin 22 as a Natural Immune Stimulant for Aquaculture

Elkins¹,

Dolan²

Authorea

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As the world population increases and wild caught fisheries decline, aquaculture offers an important sustainable solution in addressing this global challenge. However, disease management remains difficult. With limited options, there is a need for innovative solutions. The cytokine interleukin-22 (IL-22) has emerged as a possible therapeutic target for fish and has been correlated with protection under pathogen challenge. Plant-based production systems have the potential to effectively manufacture and bring unique efficacy-enhancing features to the aquaculture industry; namely, the advantages of low cost for this commodity market, ready scalability, and reduced environmental impact. Plant-expressed recombinant cfIL-22 yield and purity were adequate for in vitro activity assessment. This study serves as the first report supporting the use of plants to express therapeutic proteins with application for the aquaculture industry. Bioactivity assays showed cfIL-22 notably increased the proliferation of catfish cells, highlighting the tissue preservation capabilities of this protein. Recombinant cfIL-22 also upregulated expression of genes encoding a tissue repair protein, fibronectin, an antimicrobial peptide, Natural killer lysin-1, and a common innate immune protein, interferon. These findings support plant-made recombinant catfish interleukin-22 as a potential therapeutic for the aquaculture industry and supports further analysis of this protein for therapeutic use.

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IL-22 Induces an Acute-Phase Response Associated to a Cohort of Acute Phase Proteins and Antimicrobial Peptides as Players of Homeostasis

Cited by 3 publications

References 78 publications

Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma

Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma

A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract

Plant Production and Functional Characterization of Catfish Interleukin 22 as a Natural Immune Stimulant for Aquaculture

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