Chromogranin A-Derived Peptides Are Involved in Innate Immunity

Aslam, Rizwan; Atindehou, Ménonvè; Lavaux, Thomas; Haïkel, Youssef; Schneider, Francis; Metz‐Boutigue, Marie‐Hélène

doi:10.2174/092986712802430063

Cited by 43 publications

(38 citation statements)

References 48 publications

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“…Moreover, these are also important for inhibiting ongoing inflammatory responses. The CST, a highly conserved CgA peptide that is present in intestinal EC cells, has been described as a peptide with some immunomodulatory activities during acute experimental colitis (Rabbi et al, 2014) and restricted in vitro antibacterial activities (Aslam et al, 2012), but also antifungal and antiviral activity (Boman et al, 1993; Dorschner et al, 2001). Moreover, in a recent report, it has been observed that the CgA, the precursor of CST strongly regulates human gut microbiome (Zhernakova et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Human Catestatin Alters Gut Microbiota Composition in Mice

et al. 2017

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The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352−372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions.

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Section: Discussionmentioning

confidence: 99%

Human Catestatin Alters Gut Microbiota Composition in Mice

et al. 2017

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“…Its processed products have been shown to have a role in immunity against microbes. Aslam et al (2012) demonstrated that several antimicrobial CgA-derived peptides are able to act synergistically with antibiotics against bacteria and fungi indicating their roles in innate defense. Since t is widely held that the primary purpose of the HG is to contribute to the secretions Table 1 Mean count of mast cell.…”

Section: Discussionmentioning

confidence: 99%

Structure of the secretory cells of male and female adult guinea pigs Harderian gland

2015

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“…For example, chromagranin A-derived peptides can penetrate neutrophils, bind to cytoplasmic calmodulin, and induce Ca 2+ influx, leading to neutrophil activation and immune system augmentation [276]. …”

Section: Mechanism Of Action Of Human Antimicrobial Peptidesmentioning

confidence: 99%

Human Antimicrobial Peptides and Proteins

2014

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As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

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Chromogranin A-Derived Peptides Are Involved in Innate Immunity

Cited by 43 publications

References 48 publications

Human Catestatin Alters Gut Microbiota Composition in Mice

Human Catestatin Alters Gut Microbiota Composition in Mice

Structure of the secretory cells of male and female adult guinea pigs Harderian gland

Human Antimicrobial Peptides and Proteins

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